Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Activity involved in transfer of goods from producer to consumer or in the exchange of services.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Detailed account or statement or formal record of data resulting from empirical inquiry.
The study of animals - their morphology, growth, distribution, classification, and behavior.
The study of the structure, behavior, growth, reproduction, and pathology of cells; and the function and chemistry of cellular components.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
A standardized nomenclature for clinical drugs and drug delivery devices. It links its names to many of the drug vocabularies commonly used in pharmacy management.
Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research with the objective of cancer prevention, early stage identification and elimination. This Institute was established in 1937.
Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.
Active immunization where vaccine is administered for therapeutic or preventive purposes. This can include administration of immunopotentiating agents such as BCG vaccine and Corynebacterium parvum as well as biological response modifiers such as interferons, interleukins, and colony-stimulating factors in order to directly stimulate the immune system.
Tumors or cancer of the STOMACH.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
A malignant epithelial tumor with a glandular organization.
Treatments which are undergoing clinical trials or for which there is insufficient evidence to determine their effects on health outcomes; coverage for such treatments is often denied by health insurers.
Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.
A cell line derived from cultured tumor cells.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
The part of a human or animal body connecting the HEAD to the rest of the body.
Images used to comment on such things as contemporary events, social habits, or political trends; usually executed in a broad or abbreviated manner.
Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.
Tumors or cancer of the ANAL CANAL.
A country spanning from central Asia to the Pacific Ocean.
A malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. (Stedman, 25th ed)
Tumors or cancer of the NASOPHARYNX.
Methods to identify and characterize cancer in the early stages of disease and predict tumor behavior.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Tumors or cancer of the human BREAST.

Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines. (1/1358)

The clinical impact of dendritic cells (DCs) in the treatment of human cancer depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonstrate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macrophages (CD14+) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4. For testing the capability of RCC-antigen uptake and processing, we loaded these DCs with autologous tumor lysate (TuLy) using liposomes, after which cytometric analysis of the DCs revealed a markedly increased expression of HLA class I antigen and a persistent high expression of class II. The immunogenicity of DC-TuLy was further tested in cultures of renal tumor infiltrating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response Modifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stimulating a T cell-dependent immune response was demonstrated by: (a) the increase of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regulation of the CD3+ CD56- TcR+ (both CD4+ and CD8+) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) the enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken together, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with production of Thl cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.  (+info)

Natural variation of the expression of HLA and endogenous antigen modulates CTL recognition in an in vitro melanoma model. (2/1358)

Increasing attention has been devoted to elucidating the mechanism of lost or decreased expression of MHC or melanoma-associated antigens (MAAs), which may lead to tumor escape from immune recognition. Loss of expression of HLA class I or MAA has, as an undisputed consequence, loss of recognition by HLA class I-restricted cytotoxic T cells (CTLs). However, the relevance of down-regulation remains in question in terms of frequency of occurrence. Moreover the functional significance of epitope down-regulation, defining the relationship between MHC/epitope density and CTL interactions, is a matter of controversy, particularly with regard to whether the noted variability of expression of MHC/epitope occurs within a range likely to affect target recognition by CTLs. In this study, bulk metastatic melanoma cell lines originated from 25 HLA-A*0201 patients were analyzed for expression of HLA-A2 and MAAs. HLA-A2 expression was heterogeneous and correlated with lysis by CTLs. Sensitivity to lysis was also independently affected by the amount of ligand available for binding at concentrations of 0.001 to 1 mM. Natural expression of MAA was variable, independent from the expression of HLA-A*0201, and a significant co-factor determining recognition of melanoma targets. Thus, the naturally occurring variation in the expression of MAA and/or HLA documented by our in vitro results modulates recognition of melanoma targets and may (i) partially explain CTL-target interactions in vitro and (ii) elucidate potential mechanisms for progressive escape of tumor cells from immune recognition in vivo.  (+info)

Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells. (3/1358)

CD4(+) T cells play a critical role in generating and maintaining immune responses against pathogens and alloantigens, and evidence suggests an important role for them in antitumor immunity as well. Although major histocompatibility complex class II-restricted human CD4(+) T cells with specific antitumor reactivities have been described, no standard method exists for cloning the recognized tumor-associated antigen (Ag). In this study, biochemical protein purification methods were used in conjunction with novel mass spectrometry sequencing techniques and molecular cloning to isolate a unique melanoma Ag recognized by a CD4(+) tumor-infiltrating lymphocyte (TIL) line. The HLA-DRbeta1*0101-restricted Ag was determined to be a mutated glycolytic enzyme, triosephosphate isomerase (TPI). A C to T mutation identified by cDNA sequencing caused a Thr to Ile conversion in TPI, which could be detected in a tryptic digest of tumor-derived TPI by mass spectrometry. The Thr to Ile conversion created a neoepitope whose T cell stimulatory activity was enhanced at least 5 logs compared with the wild-type peptide. Analysis of T cell recognition of serially truncated peptides suggested that the mutated amino acid residue was a T cell receptor contact. Defining human tumor Ag recognized by T helper cells may provide important clues to designing more effective immunotherapies for cancer.  (+info)

Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours. (4/1358)

The presence of a high number of infiltrating CD1a+ cells in malignant neoplasms has been reported to be associated with an improved prognosis, reduced tumour recurrence and fewer metastases. This study identified a population of CD1a+ cells within the lymphoid cell infiltrate in human ductal breast carcinoma (n = 52), which was significantly different from normal breast tissue, in which only two out of nine cases expressed CD1a+ cells (P = 0.0192). In the majority of cases, the infiltrate was low compared with the number of macrophages and T cells present (results not shown). There was no correlation between the number of CD1a+ cells and tumour grade, with all tumour grades expressing similar numbers of infiltrating CD1a+ cells. There was clear evidence, however, that the CD1a+ cells were closely associated with tumour cells. It is likely that CD1a+ cells have a role in antigen capture and presentation in human tumours, and this study documents the density of CD1a+ cells in a large sample of all histological grades of human breast carcinomas.  (+info)

Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat. (5/1358)

These studies examined the composition of lymphocytes within the lung after the introduction of tumor cells that metastasize to the lung in rats. i.v. delivery of MADB106 tumor cells into syngeneic Fischer 344 rats caused dose- and time-dependent development of lung tumors, with surface metastases evident 7 days after injection and markedly increased 11 days after injection. The total number of lymphocytes recovered from the lung was increased 11 days after injection but not 7 days after injection. When lymphocytes from the lung, spleen, and blood were subjected to fluorescence-activated cell sorting analysis, the most conspicuous change was an increase in the percentage of CD45RA+ cells (i.e., B lymphocytes in the rat) in the lung, with no changes seen in the percentage of natural killer (NKR-P1+), CD4+, or CD8+ cells in the lung. Analysis of the time course showed that B lymphocytes increased in the lung soon after i.v. tumor injection, with an initial peak seen 6 h after injection. Rapid influx of B lymphocytes into lung after i.v. tumor cell injection was also observed in another syngeneic tumor model, i.e., after injection of CC531 cells into WAG rats. To determine whether the influx of B lymphocytes into the lung might participate in tumor surveillance, a high dose of antibody (100 microg) to rat B lymphocytes was given to immunoneutralize these cells; this produced an increase in lung tumors in both models. Finally, Fischer 344 rats were given a s.c. injection of MADB106 tumor cells that made them resistant to lung tumors when given a later i.v. injection of these tumor cells. These animals were found to have an elevated level of B lymphocytes residing in the lung associated with the resistance to lung tumor. These findings suggest that early responses of B lymphocytes are important in protection against tumor development in two rat models of cancer.  (+info)

Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion. (6/1358)

This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue.  (+info)

Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer. (7/1358)

The purpose of this review is to illustrate some of the technical and biological hurdles that need to be addressed when developing new gene therapy based clinical trials. Gene transfer approaches can be used to "mark" cells to monitor their persistence in vivo in patients, to protect cells from toxic chemotherapeutic agents, correct a genetic defect within the target cell, or to confer a novel function on the target cell. Selection of the most suitable vector for gene transfer depends upon a number of factors such as the target cell itself and whether gene expression needs to be sustained or transient. The TCR gene transfer approach described here represents one innovative strategy being pursued as a potential therapy for metastatic melanoma. Tumor reactive T cells can be isolated from the tumor infiltrating lymphocytes (TIL) of melanoma patients. A retroviral vector has been constructed containing the T cell receptor (TCR) alpha and beta chain genes from a MART-1-specific T cell clone (TIL 5). Jurkat cells transduced with this virus specifically release cytokine in response to MART-1 peptide pulsed T2 cells, showing that the virus can mediate expression of a functional TCR. HLA-A2 transgenic mice are being used to examine whether transduced bone marrow progenitor cells will differentiate in vivo into mature CD8+ T cells expressing the MART-1-specific TCR. Expression of the human TCR alpha and beta chain genes has been detected by RT-PCR in the peripheral blood of HLA-A2 transgenic mice reconstituted with transduced mouse bone marrow. Expression of the TIL 5 TCR genes in the peripheral blood of these mice was maintained for greater than 40 weeks after bone marrow reconstitution. TIL 5 TCR gene expression was also maintained following transfer of bone marrow from mice previously reconstituted with transduced bone marrow to secondary mouse recipients, suggesting that a pluripotent progenitor or lymphocyte progenitor cell has been transduced.  (+info)

Sarcomatoid renal cell carcinoma: biologic behavior, prognosis, and response to combined surgical resection and immunotherapy. (8/1358)

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2-based therapy (five patients), tumor-infiltrating lymphocyte-based therapy plus IL-2 (nine patients), high-dose IL-2-based therapy (nine patients), dendritic cell vaccine-based therapy (one patient), and interferon alpha-based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or >50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2-based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.  (+info)

Resistance to anti-cancer therapies is a consequence of adaptation of cancer cells but also of maladaptation of tumor-infiltrating immune cells. The opposing roles acquired by the immune system have to be faced in order to fight tumor growth and therapy resistance. Effector immune cells are recruited and activated but they are blocked by the strong immunosuppressive nature of the tumor microenvironment (TME). Immune evasion and deregulation of energy metabolism are two hallmarks of cancer that may be functionally linked. Malignant cells which present a high glycolytic phenotype, besides creating metabolic demanding environments that encroach on the function of tumor-infiltrating immune cells, also release immunosuppressive metabolites and by-products, such as lactate, forming a metabolic symbiosis with immune cells. This acidic TME has a strong impact in the profile of tumor-infiltrating immune cells, being instrumental for immunosuppression. Therefore, in this review, we focus on key molecular
1. Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol. 1989;142(10):3714-25 2. Baxevanis CN, Dedoussis GV. Papadopoulos NG, Missitzis I,Stathopoulos GP, Papamichail M. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. Cancer. 1994;74:1275-82 3. Chen LJ, Zheng X, Shen YP. et al. Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 2012 [Epub ahead of print] 4. Milne K, Alexander C, Webb JR. et al. Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes. J Transl Med. 2012Feb27;10:33 5. Gannot G, Gannot I, Vered H, Buchner A, Keisaris Y. Increase in immune cell infiltration with progression of oral epithelium from hyperkeratiosis to dysplasia and carcinoma. Br J Cancer. 2002;86:1444-8 6. MacLennan GT, Eisenberg R, Fleshman RL. et al. The influence of chronic ...
TY - JOUR. T1 - Tumour-infiltrating lymphocytes, programmed death ligand 1 and cyclooxygenase-2 expression in skin melanoma of elderly patients. T2 - Clinicopathological correlations. AU - Iacono, Donatella. AU - Cinausero, Marika. AU - Gerratana, Lorenzo. AU - Angione, Vito. AU - Scott, Cathryn Anne. AU - De Maglio, Giovanna. AU - Pizzolitto, Stefano. AU - Di Loreto, Carla. AU - Puglisi, Fabio. AU - Fasola, Gianpiero. AU - Minisini, Alessandro Marco. PY - 2018/12/1. Y1 - 2018/12/1. N2 - Age is an important prognostic factor in melanoma; notably, elderly patients tend to present with advanced stage skin melanoma (SM) and worse outcome. Moreover, SM is an immunogenic cancer, and its interaction with the aging immune system could have an effect on biologic behaviour of this disease. Tumour-infiltrating lymphocytes (TILs) could represent the host response in SM; it has been shown that higher grade of TILs is associated with better survival. Moreover, programmed death ligand 1 (PD-L1) and ...
Tumor-infiltrating lymphocytes, also tumour infiltrating lymphocytes, are white blood cells that have left the bloodstream and migrated into a tumor. They include T cells and B cells and are part of the larger category of tumor-infiltrating immune cells which consist of both mononuclear and polymorphonuclear immune cells, (i.e., T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, basophils, etc.) in variable proportions. Their abundance varies about tumor type and stage and in some cases relate to disease prognosis Tumor-infiltrating immune cells can often be found in the stroma and within the tumour itself. Their functions can dynamically change throughout tumor progression and in response to anticancer therapy TILs are implicated in killing tumor cells. The presence of lymphocytes in tumors is often associated with better clinical outcomes (after surgery or immunotherapy). When TILs are present, the lymphocytes are found between the ...
Tumor-infiltrating immune cells are a hallmark of most solid tumors, and the presence of varied immune populations significantly affects clinical outcomes for patients with cancer (1, 2). Historically, tumor-infiltrating immune cells have been viewed as restraining tumor progression (3), but in recent years, it has become more widely appreciated that chronic immune responses play critical roles in promoting tumor progression, metastasis, and resistance to cytotoxic therapies (1). Therefore, understanding the molecular mechanisms by which malignant cells derail antitumor immune responses to favor disease progression is critical to identify potential therapeutic targets. Recently, we reported that selective depletion of tumor-infiltrating macrophages (TAM) by neutralizing colony-stimulating factor-1 (CSF1) or inhibiting CSF1 receptor (CSF1R) activity improves the efficacy of chemotherapy in mammary tumors, in part by instigating antitumor responses by CD8+ T cells (4). Similarly, deficiency in the ...
Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node ...
Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell
Background: Tumor-infiltrating immune cells analyzed by immunohistochemistry are reported as alternative prognostic factors to supplement TNM staging in operable non-small cell lung cancer (NSCLC), but little is done by flow cytometry. Method: We established a protocol to analyze immune cells in tumor, distant lung (far from tumor) and peripheral blood mononuclear cells (PBMCs) by 8 color flow cytometry. 30 NSCLC patients with adenocarcinoma, squamous cell carcinoma and more uncommon histotypes were included and statistical analyses of cell subsets were performed. Results: We have identified the following tumor-infiltrating immune cells: CD45+ leukocytes, granulocytes, CD19+ B cells, CD4+ and CD8+ T cells with naïve/memory phenotype, CD56+CD16+ and CD56+CD16- NK cells, CD14+ macrophages, CD123+ plasmacytoid dendritic cells (pDCs), CD1c+ myeloid dendritic cells (mDCs) and CD141+ mDCs. There was an increase in leukocyte numbers in tumor compared with distant lung in adenocarcinoma. When expressed ...
AbstractImmune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear.We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8+, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions.We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome. Multivariate analysis
While breast cancer has not been considered a cancer amenable to immunotherapeutic approaches, recent studies have demonstrated evidence of significant immune cell infiltration via tumor-infiltrating lymphocytes in a subset of patient tumors. In this review we present the current evidence highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes in breast cancer. Retrospective and prospective studies have shown that the presence of tumor-infiltrating lymphocytes is a prognostic marker for higher responses to neoadjuvant chemotherapy and better survival, particularly in triple negative and HER2-positive early breast cancer. Further work is required to determine the immune subsets important in this response and to discover ways of encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative patients.
While breast cancer has not been considered a cancer amenable to immunotherapeutic approaches, recent studies have demonstrated evidence of significant immune cell infiltration via tumor-infiltrating lymphocytes in a subset of patient tumors. In this review we present the current evidence highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes in breast cancer. Retrospective and prospective studies have shown that the presence of tumor-infiltrating lymphocytes is a prognostic marker for higher responses to neoadjuvant chemotherapy and better survival, particularly in triple negative and HER2-positive early breast cancer. Further work is required to determine the immune subsets important in this response and to discover ways of encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative patients.
TY - JOUR. T1 - Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ. T2 - A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. AU - on behalf of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. AU - Dieci, Maria Vittoria. AU - Radosevic-Robin, Nina. AU - Fineberg, Susan. AU - van den Eynden, Gert. AU - Ternes, Nils. AU - Penault-Llorca, Frederique. AU - Pruneri, Giancarlo. AU - DAlfonso, Timothy M.. AU - Demaria, Sandra. AU - Castaneda, Carlos. AU - Sanchez, Joselyn. AU - Badve, Sunil. AU - Michiels, Stefan. AU - Bossuyt, Veerle. AU - Rojo, Federico. AU - Singh, Baljit. AU - Nielsen, Torsten. AU - Viale, Giuseppe. AU - Kim, Seong Rim. AU - Hewitt, Stephen. AU - Wienert, Stephan. AU - Loibl, Sybille. AU - Rimm, David. AU - Symmans, Fraser. AU - Denkert, Carsten. AU - Adams, Sylvia. AU - Loi, Sherene. AU - ...
Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer
Full Title A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN-144/ LN-145/LN-145-S1) in Patients with Solid Tumors Purpose This study is assessing an investigational immunotherapy called autologous tumor-infiltrating lymphocytes (TIL). It is made from the white blood cells (lymphocytes or T cells) that come from a piece of a patients own tumor removed during surgery. The TILs are developed further in a laboratory, then delivered back to the patient several weeks later.
Intratumoral tumor-infiltrating lymphocyte level and prominent peritumoral Crohns-like lymphoid reaction appear to be independent prognostic factors for survival in colorectal cancer, according to a study reported by Rozek et al in the Journal of the National Cancer Institute. The findings suggest that enhanced lymphocytic reaction may be associated with improved survival.. Study Details. The study involved assessment of 2,369 incident colorectal cancers from a population-based case-control study in northern Israel. Multivariate analysis for colorectal cancer-specific and overall survival included tumor-infiltrating lymphocyte level, Crohns-like lymphoid reaction, microsatellite instability, age, sex, ethnicity, grade, and stage. In grading Crohns-like lymphoid reaction, the advancing edge of the tumor was assessed for prominent inflammatory reaction, defined as a minimum of three lymphoid aggregates per section; if the advancing edge of the tumor was not present, the field was graded as ...
CD8+ tumor-infiltrating lymphocytes as a novel prognostic biomarker in lung sarcomatoid carcinoma, a rare subtype of lung cancer Jiewei Chen,1,2,* Qingmei He,2,* Jun Liu,1,2,* Yongbo Xiao,1 Canhua Xiao,3 Keming Chen,1 Dan Xie,1,2 Xinke Zhang1,2 1Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 3Department of Pathology, Qingyuan People’s Hospital, Qingyuan, 511581, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to investigate the degree of infiltration of CD8+ tumor-infiltrating lymphocytes (TILs) including high and low density in lung sarcomatoid carcinoma (LSC) and their clinicopathological significance.Patients and methods: The density of CD8+ TILs in paraffin-embedded
These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize type-1 cytokines.
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This study investigated the effects on the tumor microenvironment (TME) of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in two murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using three endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight ...
TY - JOUR. T1 - Genomic expression analysis by single-cell mRNA differential display of quiescent CD8 T cells from tumour-infiltrating lymphocytes obtained from in vivo liver tumours. AU - Zhang, Wei. AU - Ding, Jianqing. AU - Qu, Yan. AU - Hu, Hongliang. AU - Lin, Meihua. AU - Datta, Amit. AU - Larson, Alan. AU - Liu, George E.. AU - Li, Biaoru. PY - 2009/5. Y1 - 2009/5. N2 - We performed a genomic study combining single-cell mRNA differential display and RNA subtractive hybridization to elucidate CD8 T-cell quiescence/ignorance. By comparing actively maintained quiescent CD8 T cells from liver tumour tumour-infiltrating lymphocytes (TILs) with quiescent T cells at the single-cell level, we identified differentially expressed candidate genes by high-throughput screening and comparative analysis of expressed sequence tags (ESTs). While genes for the T-cell receptor, tumour necrosis factor (TNF) receptor, TNF-related apoptpsis inducing ligand (TRAIL) and perforin were down-regulated, key genes ...
The ligands and inhibitory receptors that regulate T cell effector functions are mostly overexpressed on tumor-infiltrating immune cells or on tumor cells in the tumor microenvironment. Therefore, targeting these ligands and receptors is relatively specific to tumors compared to normal tissues. It is within these tumor microenvironments that immune effector cells acquire inhibitory receptors, resulting in T cell dysfunction. Soluble molecules include cytokines with immunosuppressive activity, such as IL-10, transforming growth factor (TGF)-β, and IL-27, which regulate immune responses to tumor cells and induce T cell dysfunction within the tumor microenvironment [99-102]. The IL-10 pathway has been intensively studied for its role in T cell dysfunction in chronic viral infections and cancer [99, 100]. IL‑10 promotes T cell exhaustion, and IL‑10 blockade reverses T cell dysfunction during chronic viral infections [99]. Co-blockade of both IL-10 and the PD1 reverses CD8+ T cell exhaustion and ...
Programmed death-ligand 1 (PD-L1) testing serves as a diagnostic approach for stratifying patients with nonsmall cell lung cancer (NSCLC) and tailoring treatment. PD-L1 expression has been observed either on tumor cells or on tumor-infiltrating immune cells, but the mechanistic implications of this expression are unclear. To investigate PD-L1 expression in tumor cells and immune cells, Marcin Kowanetz et al. (pp. E10119-E10126) retrospectively characterized tumor specimens from 4,549 patients with NSCLC for PD-L1 expression. The authors found that NSCLC tumors with PD-L1 expression on tumor cells had different histological and molecular characteristics from those with PD-L1 expression on immune cells, with high PD-L1 expression on tumor cells associated with poor immune infiltration. PD-L1 expression on immune cells, with or without associated expression on tumor cells, was more prevalent and thought to reflect interferon-gamma-induced adaptive regulation. In contrast, PD-L1 expression solely on ...
Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in ...
A delicate balance between inducers and inhibitors of apoptosis exists in any given cell (37). In cancer cells, including melanoma, this equilibrium is often skewed in favor of survival, with IAPs being predominant (38, 39). Committing melanoma cells to apoptosis, which would be an ideal outcome for most therapies, therefore requires additional stimuli. Inhibition of IAPs for one can restore the balance between survival and death signals, thereby facilitating programmed cell death in melanoma.. Chronic inflammation in the tumor microenvironment of melanoma lesions often leads to elevated levels of TNF-α, at least in part, provided by the tumor-infiltrating immune cells such as macrophages (23-25). Levels of tumor-infiltrating macrophages have been shown to be associated with aggressive disease (40). All melanoma cell lines tested were resistant to treatment with exogenous TNF-α as a single agent. This was in line with previous clinical experiences, where minimal antitumor effect and ...
The immune contexture of human cancer, defined as the abundance, location and functional orientation of tumor-infiltrating immune cells [36, 37], is gaining recognition as a principal determinant of the biological and clinical behavior of many cancer types. Although it is well-established that the immune contexture may elicit both pro- and anti-tumorigenic responses, a growing body of evidence indicates that the presence of abundant tumor-infiltrating leukocytes, within established tumors, foretells favorable prognosis. This association has been rigorously documented for a number of malignancies, most notably cancers of the skin [38, 39], ovary [40, 41], colon [42-45] and breast [20-22], underscoring the broad protective effects of anti-cancer immunosurveillance [46-48].. In this work, we investigated the prognostic relevance of transcriptomic footprints of the immune contexture of breast cancer and identified both immune and biological configurations of breast cancer with distinct prognostic ...
Regulatory T cells (Tregs) can be anti-tumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients. Additionally, we investigated co-expression of immunosuppressive molecules on different Treg subsets in the TME, normal colon tissue and peripheral blood of CRC patients and healthy donors. In this preliminary study, we report that the majority of CD3+ T cells in the TME are CD4+ cells with high co-expression of PD-1/CTLA-4 and PD-1/CD39 molecules. Levels of CD4+FoxP3+Helios+ Tregs were significantly increased in the TME. Furthermore, we observed increased levels of PD-1
Gene array studies on follicular lymphoma (FL) have associated non-malignant tumor-infiltrating immune cells with patient survival. We examined the role of such cells detectable by immunohistochemistry in a tissue microarray, focusing on plasmacytoid dendritic cells (pDCs). These cells physiologically produce interferon-α, which has been used in the therapy of FL. High numbers of pDCs are associated with increased survival, and so are high numbers of CD3+ T cells. The regular distribution of pDCs within T cell areas is reflected by a weak but significant correlation between pDCs and T cells. However, in multivariate Cox models, CD123 proved to be an independent prognostic factor. These findings support the hypothesis of an association of pDCs with better prognosis by producing interferon. Furthermore, due to a linear relationship between pDCs and survival shown by means of Kaplan-Meier plots, immunohistochemical staining of CD123 could serve as a prognostic tool for patients with FL. ...
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Genentechs investigational cancer immunotherapy MPDL3280A for the treatment of PD-L1-positive non-small cell lung cancer (NSCLC) that has progressed during or after platinum-based chemotherapy (and an appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumor).. MPDL3280A (also known as anti-PD-L1) is an investigational monoclonal antibody designed to interfere with a protein called programmed death ligand 1 (PD-L1). MPDL3280A is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.. This Breakthrough Therapy designation is based on early results of MPDL3280A in patients whose NSCLC was characterized as PD-L1-positive by an ...
TY - JOUR. T1 - T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers. AU - Asaka, Shiho. AU - Yen, Ting Tai. AU - Wang, Tian-Li. AU - Shih, Ie Ming. AU - Gaillard, Stephanie. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is fundamental to developing future immune-based interventions. This study aimed to determine the immune cell populations associated with mismatch repair-deficient endometrial cancers, especially focusing on targetable regulatory pathways of the immune response. A total of 76 endometrial cancer hysterectomy specimens were evaluated for tumor-infiltrating immune cells by immunohistochemistry. Immune specific markers were used to evaluate each specimen for the number ...
To effectively and precisely fight a tumor, it is important to specifically characterize not only the cells of the tumor but also those in its microenvironment, including tumor-infiltrating immune cells. Until now, analyses of these dynamic changes with conventional biopsies and tissue sections could take days to weeks, or not occur at all prior to treatment. One alternative method is fine needle aspiration, in which only a few thousand cells are taken from different parts of a tumor and its surroundings. This method has few risks and is faster because it does not require embedding or sectioning. However, to obtain a representative estimate of the immune cell populations in the tumors microenvironment, many different stains must be carried out. Because the number of cells is so small, this means that the same sample must be repeatedly stained, destained, and stained again. However, the cells are too delicate for conventional, harsh destaining, and the procedures would take too long.. A team ...
Lung squamous cell carcinoma, which account for 25 percent of all lung cancers, have not been well characterized owing to a lack of systematic understanding of molecular pathogenesis. We performed the whole-exome and transcriptome sequencing from 101 tumors and matched normal samples from Korean patients. Somatic mutations and gene expression defined two intrinsic subtypes: (1) classical subtype; (2) immunogenic subtype. Classical subtype displayed upregulation of cell cycle related genes and enriched for gene mutations (TP53, NAV3, NFE2L2, CDKN2A, PIK2CA, KEAP1 and RB1) involved in cell proliferation, squamous differentiation and oxidative stress. Immunogenic subtype had more tumor-infiltrating immune cells than classical type. More proportion of adaptive immune cells was also detected in immunogenic subtype. Immune genes, involved in adaptive immune response, were also upregulated in immunogenic subtype. Taken together, our finding revealed that each subtype has different immune mechanisms in ...
We used proteomic and genomic analyses to identify molecular markers of pCR to neoadjuvant paclitaxel/radiation treatment. A marker of inflammation, DEFA, higher levels of tumor-infiltrating immune cells, and a microtubule-associated protein 2 (MAP2), were all found to be differentially expressed between pCR and NR tumor biopsies. To validate our findings, we showed that these markers were significantly associated with response in a separate cohort of patients receiving taxane-based neoadjuvant therapy.. Of the 38 patients enrolled in our study, 12 were triple-negative and of those 58% (7 patients) had a pCR. Only 23% of patients with non-triple-negative tumors achieved pCR. Thus, patients with triple-negative disease are twice as likely to respond to this treatment regimen. Likewise, in two independent studies, the basal-like (triple negative) and HER2+ subgroups were found to be associated with higher rates of pCR (27-45%), versus luminal pCR rates (6-7%), in patients receiving taxane-based ...
background: Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who will succumb to, and those who will eventually be cured from, their disease. This novel study: (1) evaluates the presence of different subsets of intraepithelial tumour-infiltrating lymphocytes (TILs) in lymph nodes with metastases from NSCLC patients; (2) explores the impact of intraepithelial TILs in lymph nodes on survival; (3) correlates their presence with both intraepithelial and stromal TILs in their corresponding primary tumours. methods: Metastatic lymph-node tissue from 143N+ NSCLC patients was collected and tissue microarrays were constructed. Immunohistochemistry was used to evaluate the presence of intraepithelial CD3+, CD4+, CD8+, CD20+ and CD45RO+ TILs and their ...
Background: Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC. Methods: In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression. Results: No, low, and high p53 expression was identified in 44.1% (n=299), 20.1% (n=136), and 35.8% (n=243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p|.001), high TIL levels (p=.009),
PRIMARY OBJECTIVES:. I. To validate the ability of intratumoral tumor-infiltrating T lymphocytes (TILs) to predict progression-free survival (PFS) in patients with suboptimally debulked advanced stage III or IV ovarian epithelial cancer.. II. To validate the ability of intratumoral TILs to predict PFS in patients with optimally debulked disease.. SECONDARY OBJECTIVES:. I. To validate the ability of intratumoral TILs to predict overall survival of patients with suboptimally debulked disease.. II. To validate the ability of intratumoral TILs to predict overall survival of patients with optimally debulked disease.. OUTLINE:. Patients are stratified according to status of debulked disease (suboptimal vs optimal).. Previously collected tumor tissue samples are analyzed for tumor-infiltrating lymphocytes (TIL) via immunohistochemistry and double immunofluorescence assays using standard immunostaining. ...
Background: - Metastatic digestive tract cancers, in particular esophageal, gastric, pancreatic, and liver carcinomas, have poor 5-year survival
This dose-escalation study investigated the tolerability and efficacy of adoptive transfer of CH 296 (RetroNectin)-induced T-cell therapy in patients with
Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as tumor-infiltrating lymphocytes, which a posteriori locate within the tumor tissues. Although such cells can be found, the …
Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma in Situ, Metastatic Tumor Deposits and Areas for Further Research Academic Article ...
This phase I trial will evaluate the side effects and the best dose of nivolumab when given together with gene-modified T cells and vaccine therapy in treating
Tumor-infiltrating lymphocytes (TILs) automatic immunohistochemical evaluation. Free app for Windows systems. OIQ software sample images
Cooper ZA, Frederick DT, Juneja VR, Sullivan RJ, Lawrence DP, Piris A, Sharpe AH, Fisher DE, Flaherty KT, Wargo JA. BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes. Oncoimmunology. 2013;2 (10) :e26615.
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8+ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8+ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8+ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8+ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8+ lymphocytes, ...
Early trials using polyclonal T cells extended from tumour-infiltrating lymphocytes confirmed amazing response rates in patients with melanoma prior to the era of icis36. ways of potentially overcome obstacles to T cell activation also to enhance the efficiency of immunotherapy are dealt with. turned on, tumour-specific T cells within an adoptive cell treatment approach. Early studies using polyclonal T cells extended from tumour-infiltrating lymphocytes confirmed impressive response prices in sufferers with melanoma prior to the period of icis36. Newer iterations of these cellular therapies are the use of customized T cells which have been genetically built to identify tumour cells. Such technology consist of chimeric antigen receptor T cells, which contain the guarantee to revolutionize the treating hematologic malignancies37. Tumour regression in addition has been attained in solid tumours using T cells which are built expressing a high-affinity tcr that identifies a peptide produced from a ...
原発性乳癌における腫瘍浸潤リンパ球(TILs)関連遺伝子マーカーは化学療法の治療効果を予測す ...
T cells expressing chimeric antigen receptors (CAR T cells) targeting human CD19 (hCD19) have shown clinical efficacy against B cell malignancies1,2. CAR T cells have been less effective against solid tumours3-5, in part because they enter a hyporesponsive (exhausted or dysfunctional) state6-9 triggered by chronic antigen stimulation and characterized by upregulation of inhibitory receptors and loss of effector function. To investigate the function of CAR T cells in solid tumours, we transferred hCD19-reactive CAR T cells into hCD19+ tumour-bearing mice. CD8+CAR+ tumour-infiltrating lymphocytes and CD8+ endogenous tumour-infiltrating lymphocytes expressing the inhibitory receptors PD-1 and TIM3 exhibited similar profiles of gene expression and chromatin accessibility, associated with secondary activation of nuclear receptor transcription factors NR4A1 (also known as NUR77), NR4A2 (NURR1) and NR4A3 (NOR1) by the initiating transcription factor NFAT (nuclear factor of activated T cells)10-12. CD8+ T
The Young Oncologists Journal Club is an initiative from the European Society from Medical Oncology. Read the latest article on breast cancer.
Balermpas, Panagiotis; Roedel, Franz; Roedel, Claus; Krause, Mechthild; Linge, Annett; Lohaus, Fabian; Baumann, Michael; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Avlar, Melanie; Grosu, Anca-Lidia; Abdollahi, Amir; Debus, Juergen; Bayer, Christine; Stangl, Stefan; Belka, Claus; Pigorsch, Steffi; Multhoff, Gabriele; Combs, Stephanie E.; Moennich, David; Zips, Daniel; Fokas, Emmanouil ...
TY - JOUR. T1 - Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2. AU - Arienti, Flavio. AU - Belli, Filiberto. AU - Rivoltini, Licia. AU - Gambacorti-Passerini, Carlo. AU - Furlan, Luigi. AU - Mascheroni, Luigi. AU - Prada, Augusto. AU - Rizzi, Maurilia. AU - Marchesi, Edoardo. AU - Vaglini, Maurizio. AU - Parmiani, Giorgio. AU - Cascinelli, Natale. PY - 1993/9. Y1 - 1993/9. N2 - Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogeneic tumor cells. A preferential lysis of autologous melanoma cells was obtained in ...
Previous studies identified a prominent role of S1PR1 in tumor progression linked to persistent STAT3 activation in tumor and myeloid cells (Lee et al., 2010; Deng et al., 2012; Degagné et al., 2014). We previously noticed STAT3 signaling downstream of S1PR1 in human macrophages, which contributed to establishing an anti-inflammatory phenotype (Weis et al., 2009). However, in the present study, S1PR1 signaling in CD11bhi CD206+ TAMs did not affect typical STAT3 target genes in macrophages. Rather, a so-far-unexplored S1PR1 signaling circuit in macrophages promoted lymphangiogenesis via NLRP3-dependent IL-1β secretion.. Our global mRNA expression data in TAMs failed to identify previously described macrophage-derived prolymphangiogenic factors such as VEGF-C or VEGF-D as targets of S1PR1 signaling (Kerjaschki, 2005). Rather, NLRP3 expression and the concomitant IL-1β release promoted lymphangiogenesis. Although an involvement of VEGFs in the prolymphangiogenic properties of TAMs in breast ...
TY - JOUR. T1 - Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma. AU - Kawakami, Yutaka. AU - Dang, Nita. AU - Wang, Xiang. AU - Tupesis, Janis. AU - Robbins, Paul F.. AU - Wang, Rong Fu. AU - Wunderlich, John R.. AU - Yannelli, John R.. AU - Rosenberg, Steven A.. PY - 2000/2/15. Y1 - 2000/2/15. N2 - A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established from patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in the Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase, MART-1/melan-A, gp100, TRP1, TRP2) as well as peptides derived from MAGE-1 and MAGE-3. Examination of the specificity of these T cells indicated that 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TIL, and 27% of HLA-A31 TIL recognized shared melanoma antigens restricted by major ...
The tumor immune microenvironment (TIME) is the cellular environment in which tumors exist. This includes: surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, immune checkpoint proteins and the extracellular matrix (ECM). The TIME plays a critical role in cancer progression and regulation. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. The molecules and cells in the TIME influence disease outcome by altering the balance of suppressive versus cytotoxic responses in the vicinity of the tumor. Having a better understanding of the tumor immune microenvironment will pave the way for identifying new targets for immunotherapies that promote cancer elimination.
In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population ...
TY - JOUR. T1 - Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images. AU - The Cancer Genome Atlas Research Network. AU - Saltz, Joel. AU - Gupta, Rajarsi. AU - Hou, Le. AU - Kurc, Tahsin. AU - Singh, Pankaj. AU - Nguyen, Vu. AU - Samaras, Dimitris. AU - Shroyer, Kenneth R.. AU - Zhao, Tianhao. AU - Batiste, Rebecca. AU - Van Arnam, John. AU - Caesar-Johnson, Samantha J.. AU - Demchok, John A.. AU - Felau, Ina. AU - Kasapi, Melpomeni. AU - Ferguson, Martin L.. AU - Hutter, Carolyn M.. AU - Sofia, Heidi J.. AU - Tarnuzzer, Roy. AU - Wang, Zhining. AU - Yang, Liming. AU - Zenklusen, Jean C.. AU - Zhang, Jiashan (Julia). AU - Chudamani, Sudha. AU - Liu, Jia. AU - Lolla, Laxmi. AU - Naresh, Rashi. AU - Pihl, Todd. AU - Sun, Qiang. AU - Wan, Yunhu. AU - Wu, Ye. AU - Cho, Juok. AU - DeFreitas, Timothy. AU - Frazer, Scott. AU - Gehlenborg, Nils. AU - Getz, Gad. AU - Heiman, David I.. AU - Kim, Jaegil. AU - Lawrence, Michael S.. AU - ...
Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) achieved impressive clinical results with response rates of up to 50% in patients with metastatic melanoma.. Previous trials investigating TIL therapy for patients with renal cell carcinoma (RCC) have shown limited success, however none of these early trials used current TIL manufacturing methods and preparative chemotherapy regimens. RCC is an obvious candidate for implementation of TIL therapy because of its known immunogenicity. ...
Tumour infiltrating lymphocytes influence colorectal cancer (CRC) progression. However, lymphocyte infiltration comes in different flavours and evidence has been provided that the spatial distribution of immune cells within the tumour tissue is an important immunological feature. The aim of this thesis was to investigate how the dual localization of tumour infiltrating lymphocytes (TILs) can affect their function in the tumour microenvironment. The project started with the analysis of the CD3 compartment, as CD3+ T cell infiltration (CD3-TILs) is a recognized positive prognostic factor for CRC patients. Results here presented show that CD3+ tumour-infiltrating lymphocytes are present both interspersed in the tumour tissue or scattered throughout the stroma (CD3-TILs) and also aggregated in lymphoid structures showing features of tertiary lymphoid tissue (CD3-TLT). Tumour-associated TLT had a peculiar compartmentalization, with CD3+ T cells and CD20+ B lymphocytes holding complementary positions ...
Major players of the cancer-related inflammation are chemokines and their receptors. Fractalkine (CX3CL1) is a peculiar chemokine, existing both as a soluble and a membrane-anchored protein. Its unique receptor, CX3CR1, is expressed on monocytes, NK, and T cells. In this study we provide evidence that CX3CL1 is expressed in human colorectal carcinoma and may modulate tumor malignant behaviour. CX3CL1 mRNA expression, evaluated in 30. CRC samples Selleckchem Bafilomycin A1 was strongly up-regulated in tumor tissues in comparison to normal colonic mucosa. CX3CL1 Serine/threonin kinase inhibitor protein expression has been evaluated by immunohistochemistry in 172 CRC samples, classified by tumor stage, confirming a strong positivity by tumor cells. On the same series of samples, the expression of CD3 and CD68 is being investigated by immunohistochemistry and the density of tumor-infiltrating T lymphocytes and macrophages will be associated with the expression score of CX3CL1, as well as with ...
We have previously reported the TCR inhibitory molecule CD5 impairs reactivity of tumor-specific PBL-derived T-cell clones against the cognate target and controls their susceptibility to activation-induced cell death (AICD) triggered by tumor cells. In this report, we compared the antitumor T-cell response developed against the B16F10 melanoma engrafted in CD5-deficient and wild-type (wt) C57BL/6 mice. Our results indicate that CD5 knock out mice elicit a delayed tumor growth as compared to wt mice, which is associated with tumor infiltration by more activated tumor-reactive T lymphocytes. Our data also indicate that tumor suppression in CD5-deficient mice is transient and that tumor flare up correlates with increase in AICD of tumor-infiltrating CD8+ T cells. Our data suggest that tumor T lymphocyte infiltration occurs at early stages of cancer development and that tumor-mediated AICD is most likely involved in the induction of T-cell tolerance to malignant cells. ...
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TY - JOUR. T1 - MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas. AU - Housseau, Franck. AU - Zeliszewski, Dominique. AU - Roy, Maguy. AU - Paradis, Valerie. AU - Richon, Sophie. AU - Rigour, Alice. AU - Bougaran, Joelle. AU - Prapotnich, Dominique. AU - Vallancien, Guy. AU - Benoit, Gérard. AU - Desportes, Laurent. AU - Bedossa, Pierre. AU - Hercend, Thierry. AU - Bidart, Jean Michel. AU - Bellet, Dominique. PY - 1997/6/19. Y1 - 1997/6/19. N2 - Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell ...
Lion Biotechnologies, Inc. (Nasdaq: LBIO), a biotechnology company that is developing novel cancer immunotherapies based on tumor infiltrating lymphocytes (TIL), today announced that researchers from Moffitt Cancer Center reported positive results from a pilot trial of TIL and ipilimumab in patients with metastatic melanoma. The data from the trial, which Lion partially sponsored, were presented at the Society of Surgical Oncology 2015 meeting in Houston, TX on Friday, March 27, 2015.. The Phase 1 trial was conducted at Moffitt Cancer Center in 12 patients with metastatic melanoma, with the objective of determining the safety and feasibility of combining TIL therapy with the CTLA-4 checkpoint inhibitor, ipilimumab. Patients were treated with ipilimumab one week prior to tumor harvest for TIL expansion, a second time while their TIL were being expanded, and two more times following TIL transfer.. Of the 12 patients enrolled in the trial, 11 went on to receive their autologous TIL, with five out ...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic ...
Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression
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© The Author(s) 2016. A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more
The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell-deficient mice progressed and killed all of the animals. Adoptive transfer of tumor antigen-experienced T cells eliminated Pik3ca-null tumors in immunodeficient mice. Loss of PIK3CA or inhibition of its effector AKT increased the expression of MHC class I and CD80 on tumor cells. These changes contributed to the increased susceptibility of Pik3ca-null tumors to T cell surveillance. Our results indicate that tumor cell PIK3CA-AKT signaling ...
Background: B7-H4, a member of the B7 family, is involved in the regulation of antigen-specific immune responses. Here we addressed its expression in non-small-cell lung cancer (NSCLC) pathology and correlation to the number of CD3+ tumor infiltrating T-lymphocytes in invasive carcinomas. We also observe the effects of B7-H4 gene expression on cell proliferation and migration in the human NSCLC cell line.. Methods: B7-H4 expression was evaluated by immunohistochemistry in 102 patients with NSCLC who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. B7-H4 shRNA was cloned into pGCsi-U6/Neo plasmid and the product was transfected into A549 cells with Lipofectamine 2000.. Results: B7-H4 is transcripted in three cell lines. In tumor tissues, expression of B7-H4 is found both in the cell membrane and in the cytoplasm. B7-H4 transfection vector-pGCshB7-H4 was successfully constructed. After transfected ...
T cell dysfunction is a hallmark of many cancers, but the basis for T cell dysfunction and the mechanisms by which antibody blockade of the inhibitory receptor PD-1 (anti-PD-1) reinvigorates T cells are not fully understood. Here we show that such therapy acts on a specific subpopulation of exhausted CD8+ tumor-infiltrating lymphocytes (TILs). Dysfunctional CD8+ TILs possess canonical epigenetic and transcriptional features of exhaustion that mirror those seen in chronic viral infection. Exhausted CD8+ TILs include a subpopulation of progenitor exhausted cells that retain polyfunctionality, persist long term and differentiate into terminally exhausted TILs. Consequently, progenitor exhausted CD8+ TILs are better able to control tumor growth than are terminally exhausted T cells. Progenitor exhausted TILs can respond to anti-PD-1 therapy, but terminally exhausted TILs cannot. Patients with melanoma who have a higher percentage of progenitor exhausted cells experience a longer duration of response to
In recent years, the search for new cancer treatments has increasingly focused on immunotherapies that harness the bodys own defenses to fight tumors. Adoptive cell therapy (ACT) is a powerful immunotherapeutic strategy that can effectively control some cancers but that also has drawbacks.
The new generation of antibodies emerges as an alternative to cancer treatment. The therapy is based on modulation and activation of immune cells, increasing the survival of many patients and, leading to long-term remission. The mechanism consists of blocking molecules that halt T cell activation, such as PD-1, PD-L1, and CTL-4, making the immune system more effective, and working against cancer.The immune-checkpoint blockade therapy (ICB) has been introduced in many anti-cancer treatments, even associated with other drug schedules, which is a new promising therapy option. However, the benefits of ICB are not efficient for all patients. Due to overactivation of the immune system, it can induce a high number of adverse effects such as colitis, hepatitis, adrenocorticotropic hormone insufficiency, which therefore increase morbidity and mortality.Why is the ICB not effective for some patients? What factors are involved in the success of the therapy? How could we predict which patients would over-activate
Phenotyping TILs in situ: The enumeration and quantitation of phenotypic subsets of immune cells in tissue sections. Tuesday, September 10, 2013 , 9:00 am Pacific , 12:00 pm Eastern , 5:00 pm GMT. Presenter: James Mansfield, Director -Tissue Analysis Applications, PerkinElmer. In many cancers, tumor-infiltrating lymphocytes (TILs) indicate levels of tumor immunogenicity and predict survival. In particular, increased levels of regulatory T-cells (Tregs) are associated with poorer prognosis, while CD69+ T-cells may also be prognostic. Understanding the phenotype and pattern of TILs in situ within tumors would be advantageous. However, visual TIL assessment cannot easily determine the type of lymphocyte in situ, and multimarker quantitation is difficult with standard methods. We present a multi-marker, computer-aided event-counting method for determining the phenotypes of lymphocytes in a range of tumor types using a multispectral imaging (MSI) automated tissue segmentation and counting ...
Cancer-associated macrophages have been studied for quite some time, but how they turned from good macrophages to bad macrophages was still unclear. The recent publication of Victoria Sanz-Moreno et al. from the Kings College of London on Cell has answer a lot of questions.. ROCK-Myosin II is well known to regulate amoeboid migration during invasion and metastasis. In an outstanding publication in Cell, Sanz-Moreno and colleagues have been able to identify how melanoma cells sitting at the leading edge of the tumor are able to control an immunomodulatory secretome mechanism that not only attracts monocyte to this site, but forces them to differentiate into cancer-associated macrophages promoting tumor growth. In fact, these amoeboid tumor cells present high levels of ROCK-Myosin activity, which is the master regulator of the immunomodulatory secretome.. ...
Recent work has shown that the immune microenvironment plays an important role in tumor biology. Here, Coussens and colleagues show that infiltration of certain types of leukocytes into breast tumor tissue predicts patient survival. In particular, high levels of CD8+ CTLs correlated with good outcome, whereas high levels of CD4+ T lymphocytes and TAMs correlated with poor outcome. Further, the authors found that the immune signature was predictive of relapse-free survival in patients whose disease had spread to their lymph nodes. Because such patients are often treated with chemotherapy, the authors hypothesized that the immune microenvironment might play a role in chemosensitivity. In a mouse model, they demonstrated that recruitment of TAMs was a common response of breast cancers to cytotoxic agents. The authors next demonstrated that treatment of tumor-bearing animals with antibodies or a small molecule that inhibited recruitment of TAMs resulted in improved sensitivity to chemotherapy as ...
Tumor-infiltrating dendritic cell subsets of progressive or regressive tumors induce suppressive or protective immune responses. - Yongqing Liu, Xuguang Bi, Shulin Xu, Jim Xiang
Adoptive immunotherapy (AIT) involving transfer of tumor-sensitized T lymphocytes in combination with cyclophosphamide (CY)-injection results in the eradication of the C57BL/6J (B6) rhabdomyosarcoma, 76-9 and is associated with the accumulation of a large number of tumor-infiltrating lymphocytes (TIL). Using immune spleen cells (ISC) from B6 and congenic B6. PL. Thy-1a mice, it was shown that most (| or = 97%) of the TIL were donor-derived. This in situ increase in donor-derived T cells was confirmed by using positively-selected Thy- 1.1+ and Thy- 1.2+ TIL for AIT after isolating them from regressing tumors and expanding them in rIL-2. The extent of CD8+ TIL expansion in vivo correlated with the numbers of TIL adoptively transferred and this in turn determined the degree of anti-tumor effects. It was evident, however, that these in vitro-expanded TIL expressing mRNA for TNF alpha and IFN gamma were qualitatively different and therapeutically less efficacious than the T cells associated with
Tumor-infiltrating lymphocytes (TILs) have a strong prognostic and predictive significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs). Here, we performed histologic analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs, and their prognostic significance in TNBC. We retrospectively analyzed 769 patients with TNBC. TILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion rate, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumor stroma, high levels of peritumoral lymphocytic infiltration, and moderate to abundant TLSs in adjacent tissue. TILs, degree of ...
Chow et al. demonstrated that CXCR3 expression on intratumoral CD8+ T cells, and the expression of its ligand, CXCL9, by intratumoral CD103+ DCs was required for the efficacy of PD-1 blockade. Anti-PD-1 expanded CXCR3+CD8+ T cells within MC38 tumors in mice and increased CXCL9 and CXCL10 production by DCs, leading to an enhanced antitumor response, likely via more frequent DC-T cell interactions. Across solid murine tumors, baseline intratumoral expression of CXCR3 ligands correlated with response to PD-1 blockade. In melanoma patients treated with anti-PD-1, early post-treatment levels of CXCR3 ligands correlated with response.
Most research to date pertaining to neural influence on immune response involves immunosuppression via the anti-inflammatory pathway. However, there is emerging evidence indicating that neurotransmitters have the ability to promote immune activation. We are investigating whether neurotransmitters can modulate and/or activate T cell function in situations where immunosuppression is prevalent such as in the tumor microenvironment. Published work suggests that glutamate, serotonin, dopamine, and Substance P trigger immune responses such as cytokine secretion, integrin expression, and chemotaxis. We saw that both CD4 and CD8 T cells express high surface protein levels of glutamate receptor AMPA iGluR3, which is able to import Ca2+ and Na+. We also found that mGluR1 is significantly upregulated on lymphocytes upon activation. Our data further show that T cells in the tumor-draining LN and tumor-infiltrating lymphocytes have upregulated expression of iGluR3 and mGluR1. Treatment with glutamate or its ...
BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, ...
BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, ...
BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, ...
BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, ...
BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, ...
Beckman Coulter Life Sciences examines the differences between TCRs (T-cell receptors), TILs (tumor-infiltrating lymphocytes), and CAR-Ts (chimeric antigen receptor-T cells) in immunotherapy.
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others ...
OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis ...
Tumor-infiltrating lymphocytes can help the bodys immune system fight cancer, which is why the presence of CD8 could come with positive survival rates. This could ultimately help doctors determine more specific survival risks for tumors that are now lumped together as once group, with the group usually called aggressive. Basal-like tumors with CD8 might not be aggressive at all. The positive prognosis did not extend to non-basal tumors ...
A number of trials of immune checkpoint inhibitors, both as monotherapy and in combination with other therapies, have been reported. While response rates with monotherapy in the advanced stage setting are relatively low, the durability of responses observed is remarkable. While PD-L1 positivity enriches for responders, it is not a consistent predictor of response. Response appears to correlate more strongly with tumor-infiltrating lymphocyte (TIL) density ...
The company works to develop tumor-infiltrating lymphocyte (TIL) therapies against cancer. The company was founded in 2007 as ... "Pursuit of tumor-infiltrating lymphocyte immunotherapy speeds up". Nature Biotechnology. Retrieved 14 August 2019. Adelman, ...
With T-cell FluoroSpot, you can monitor tumor-infiltrating lymphocytes. You can also analyze the IFN-y cytokine and granzyme B ... With the ELISpot, you can study antigen-specific cytokine responses, antibody specific secreting cells, tumor antigens, ...
Tumor counterattack: Tumors may over-express Fas ligand and induce the apoptosis of infiltrating lymphocytes, allowing the ... "Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes". Nat Commun. 8 (1): 1404. Bibcode: ... "Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors". Nat Med. 20 (6): 607-15. doi: ... Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (May 1999). "A newly identified member of tumor necrosis factor receptor ...
"Chapter 18: Flow Cytometric Identification of Tumor-Infiltrating Lymphocytes from Glioblastoma." In: Methods in Molecular ... "Immune Complement of Patients with Brain Tumors." In: Translational Immunotherapy of Brain Tumors. Sampson JH (ed.), 2017, ... Fecci has curated a body of research focused on brain tumor immunology and immunotherapy. In this area, he wrote his first ... Towards the mid 2000s, his research began focusing on T cell dysfunction in brain tumor patients. In 2006, he published a paper ...
Zhu J, Petit PF, Van den Eynde BJ (2018). "Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism". ... "Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes". Nat Commun. 8 (1): 1404. doi: ... "Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors". Nat Med. 20 (6): 607-15. doi: ... In oncology, this blockade is intended to prevent the killing of activated T cells that can be induced by tumor-associated ...
Lymphocytes infiltrating the stroma of growing, transplantable tumors provided a concentrated source of tumor-infiltrating ... "Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy". Journal of ... The adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) or genetically re-directed peripheral blood ... They destroy the tumors in the sample within 2 to 3 weeks. They then produce pure cultures of lymphocytes that can be tested ...
... technology using yeast-displayed peptide-MHC molecules to identify tumor antigens recognized by Tumor Infiltrating Lymphocytes ... "Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes". Cell. 172 (3): 549-563.e16. ... such as those resident in tumors. This technology also enabled a breakthrough in understanding how signaling is initiated by ...
On the other hand, CCL17 will also activate tumor-infiltrating lymphocytes tumors. For many cancers, the more CCL17 in the area ... CCL17 is known to help lymphocytes target areas on the skin, and could play a role in treatment of dermatitis and of other ... Some cancers that form tumors, such as breast cancer, produce CCL17 which draws T regulatory cells into the area, enhancing the ... "CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and ...
Moreover, macrophages infiltrating the tumor microenvironment can transition towards a regulatory phenotype. Regulatory ... macrophages produce Interleukin 10, which can inhibit cytotoxic responses of other lymphocytes to cancer cell antigens. The ... Tumor-associated macrophages may be any of these types, and they have been found to be important players in the tumor ... Jan 23, 2013). "Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic ...
A dysgerminoma is a type of germ cell tumor; it usually is malignant and usually occurs in the ovary. A tumor of the identical ... Dysgerminoma characterized by uniform cells separated by fibrous septa with lymphocytes, H&E stain. Low-power view of a ... dysgerminoma infiltrating the colonic wall, H&E stain. Dysgerminomas, like other seminomatous germ cell tumors, are very ... "Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary ...
29 October 2013). "Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer". British Journal ... Also, there is an association between an increase in tumour-infiltrating lymphocytes and in circulating white blood cells in ... This results in a HPV+OPC tumour being given a lower stage than if it were HPV-OPC. For instance, a 5 cm tumour with one ... The pRb protein is inactivated by E7 in HPV+OPC, but in HPV-OPC it is the p16 tumour suppressor part of the pRb tumour ...
"A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma". Cancer Research. ... "Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells". ...
October 2012). "Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic ... The extraction of G-CSF lymphocytes from the blood and expanding in vitro against a tumour antigen before reinjecting the cells ... These cells are then either pulsed with an antigen or tumor lysate or transfected with a viral vector, causing them to display ... March 2005). "CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally ...
"ASCO Annual Meeting Proceedings Part I. Abstract: Protective effect of a brisk tumor infiltrating lymphocyte infiltrate in ... tumor-infiltrating lymphocytes) isolated from a person's own melanoma tumor.[108] These cells are grown in large numbers in a ... Sentinel lymph node biopsy is often performed, especially for T1b/T2+ tumors, mucosal tumors, ocular melanoma and tumors of the ... which is judged by the presence and activity of the tumor infiltrating lymphocytes (TILs). These cells sometimes completely ...
Tumor-infiltrating lymphocytes are a key for clinical outcomes and prediction of the response to checkpoint inhibitors. In vivo ... The TAMs have opposite effects; M1 for anti-tumor activities, and M2 for pro-tumor activities. Oghumu et al clarified that ... Production by Tumor Cells Is Critical for T Cell-Mediated Suppression of Cutaneous Tumors". The Journal of Immunology. 178 (4 ... show anti-tumor effect against cancer cells through paracrine CXCL9/CXCR3 in tumor models. The autocrine CXCL9/CXCR3 signaling ...
1993). "Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell ... but is not produced by normal lymphocytes. A study also demonstrate how the autocrine production of the IL-7 cytokine mediated ... and may serve as a regulatory factor for intestinal mucosal lymphocytes.[citation needed] Knockout studies in mice suggested ... 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes". J. Clin ...
... period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes". Clin. ... with an aim of inducing the lymphocytes which will carry their activity of destroying the tumour cells. Thereafter the adverse ... June 2002). "Prognostic significance of adoptive immunotherapy with tumor-associated lymphocytes in patients with advanced ... Upon encountering a tumor cell, the activated NK cell attaches to the membrane of the cancer cell and injects toxic granules ...
... mastocytosis and tumor infiltrating lymphocytes. It functions as the receptor for HTLV-1 and is consequently expressed on ... Mouse CD Antigen Chart Human CD Antigen Chart CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth ...
"Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes". J ...
1994). "Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor ... 1998). "Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocyte (CTL ... 1997). "Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas". Am. J. Pathol. 150 ( ...
... mitogenic stimulation of human tumor-infiltrating lymphocytes". Biochim. Biophys. Acta. 1269 (1): 41-50. doi:10.1016/0167-4889( ... Packard BZ, Lee SS, Remold-O'Donnell E, Komoriya A (1995). "A serpin from human tumor cells with direct lymphoid ...
This causes large numbers of tumor-infiltrating lymphocytes (TILs) to be found in the tumor microenvironment. Although it is ... Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (June 2011). "The prognostic influence of tumour-infiltrating lymphocytes ... Most tumors elicit an immune response in the host that is mediated by tumor antigens, thus distinguishing the tumor from other ... it is thought that these lymphocytes target cancerous cells and therefore slow or terminate the development of the tumor. ...
... containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes". J. Immunol. 166 (4): 2871-7. doi: ...
... using tumor-infiltrating lymphocytes modified by retroviral gene transduction". The New England Journal of Medicine. 323 (9): ... The goal was to cure malignant brain tumors by using recombinant DNA to transfer a gene making the tumor cells sensitive to a ... One possible solution is to add a functional tumor suppressor gene to the DNA to be integrated. This may be problematic since ... October 1995). "T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years". Science. 270 (5235): ...
Transferred immunological components include immune cells such as T lymphocytes or tumour-infiltrating lymphocytes, NK cells, ...
"Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating ...
"Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma". J. ... The extraction of G-CSF lymphocytes from the blood and expanding in vitro against a tumour antigen before reinjecting the cells ... These cells are then either pulsed with an antigen or tumor lysate or transfected with a viral vector, causing them to display ... The cells are then reinfused and produce an immune response against the tumour cells.[16] The technique has been tested on ...
"T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of ... A team at the Roswell Park Cancer Institute showed that CD8+ Tumor-infiltrating lymphocytes that were specific for NY-ESO-1 ... Also in 2001 the Triebel group reported finding LAG3 expression on CD8+ tumor-infiltrating lymphocytes, with this LAG3 ... "Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific ...
... using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med., 323: 570-578,1990. Rosenberg, ... Mullen, C.A., Snitzer, K., Culver, K.W., Morgan, R.A., Anderson, W.F., Blaese, R. M.: Molecular analysis of T lymphocyte- ... A thorough immune status follow-up was done after 12 years: she remained healthy with 20% of her lymphocytes still carrying an ... T lymphocyte-directed gene therapy for ADA deficiency SCID: Initial trial results after 4 years. Science. 270: 475-480, 1995. ...
... may refer to: Tumor-infiltrating lymphocytes TRNAIle-lysidine synthase, an enzyme This disambiguation page lists articles ...
... which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a ... We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour ... This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and ... There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearmans rank correlation = ...
The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other ... N2 - The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and ... AB - The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and ... abstract = "The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden ...
Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma ... A Phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in ... A Phase 1 Dose Escalation Study to Assess Safety and Efficacy of ADP-A2M4CD8 in HLA-A2+ Subjects with MAGE-A4 Positive Tumors ... Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial PLATFORM ...
Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma ... A Phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in ... A Phase 1 Dose Escalation Study to Assess Safety and Efficacy of ADP-A2M4CD8 in HLA-A2+ Subjects with MAGE-A4 Positive Tumors ... Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial PLATFORM ...
Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma ... A Phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in ... A Phase 1 Dose Escalation Study to Assess Safety and Efficacy of ADP-A2M4CD8 in HLA-A2+ Subjects with MAGE-A4 Positive Tumors ... Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial PLATFORM ...
Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma ... A Phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in ... A Phase I Study of GNX102 in Patients with Advanced Solid Tumors This new medicine, GNX102, is an antibody that binds to a ... A Phase 1 Dose Escalation Study to Assess Safety and Efficacy of ADP-A2M4CD8 in HLA-A2+ Subjects with MAGE-A4 Positive Tumors ...
MaSTherCell will manufacture tumour infiltrating lymphocyte for Iovance ... MaSTherCell will manufacture tumour infiltrating lymphocyte for Iovances European late-stage clinical trials ... Biotherapeutics is a biotechnology company developing novel cancer immunotherapies based on tumour infiltrating lymphocyte (TIL ... By addressing the unmet needs for solid tumor treatment, the outcome of this project could represent an enormous hope for a ...
The treatment, known as tumor-infiltrating lymphocyte therapy, or TIL, is a testament to how far modern science has evolved. ... With this therapy, doctors remove a tumor and harvest special immune cells that are found naturally in the tumor. Doctors then ... Not only had no new tumors developed, but the six existing tumors in her lungs had shrunk significantly. Less than a year after ... On April 1, 2015, Ryan had her tumor removed at the NIH. Two months later, she went inpatient for four weeks to have the team " ...
Iovance Biotherapeutics Initiates Clinical Supply of Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy Manufactured at Iovance ...
The treatment, known as tumor-infiltrating lymphocyte therapy, or TIL, is a testament to how far modern science has evolved. ... With this therapy, doctors remove a tumor and harvest special immune cells that are found naturally in the tumor. Doctors then ... Not only had no new tumors developed, but the six existing tumors in her lungs had shrunk significantly. Less than a year after ... On April 1, 2015, Ryan had her tumor removed at the NIH. Two months later, she went inpatient for four weeks to have the team " ...
The treatment, known as tumor-infiltrating lymphocyte therapy, or TIL, is a testament to how far modern science has evolved. ... With this therapy, doctors remove a tumor and harvest special immune cells that are found naturally in the tumor. Doctors then ... Not only had no new tumors developed, but the six existing tumors in her lungs had shrunk significantly. Less than a year after ... On April 1, 2015, Ryan had her tumor removed at the NIH. Two months later, she went inpatient for four weeks to have the team " ...
Assessing tumor-infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized ... Assessing tumor-infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized ... An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH and Jiang WQ: Elevated neutrophil to lymphocyte ratio predicts ... Chiang SF, Hung HY, Tang R, Changchien CR, Chen JS, You YT, Chiang JM and Lin JR: Can neutrophil-to-lymphocyte ratio predict ...
... tumor-infiltrating Treg generally show potent suppressive functions, indicating that they regulate tumor-specific immune ... These Treg-related cell markers include CD27 [20], CD62L [21], CTLA4 (cytotoxic T-lymphocyte-associated protein) [22], CD39 and ... Cell surface expression of TNFR2 not only identifies the potent Treg subsets but also is the property of tumor-infiltrating ... thus facilitating tumor immune escape. That TNFR2 knockout mice show improved immune responses to tumors might be caused by the ...
... of Innate lymphoid cells that play a key role in immunoregulation and limit the expansion of tumour-infiltrating lymphocytes. ... My group has developed the ability to grow tumour-infiltrating T cells, characterize their properties and develop therapies ... Keywords: immune surveillance, tumour immunity, autoimmunity, T cell activation, immunotherapy, immune tolerance ...
... understanding the relationships between T cell specificities and the cellular states of tumor-infiltrating T lymphocytes in ... Within the tumor microenvironment of PDAC, I discovered that hypoxia induces a transient metastatic program in cancer cells ( ... While most of his lab focuses on lung cancer, I focused my investigations on the tumor microenvironment in pancreatic ductal ... After focusing on cancer cell-intrinsic changes induced by the PDAC tumor microenvironment, I then pursued a short second ...
... tumour infiltrating lymphocytes therapy for metastatic melanoma; and (2) high-dose chemotherapy for BRCA1-like subgroup in ...
Musculoskeletal Tumors. Singla, A. & Geller, D. S., Feb 2020, In: Pediatric clinics of North America. 67, 1, p. 227-245 19 p.. ... To B(MP-2) or Not To B(MP-2): Cytokines and tumor surgery-letter. Geller, D. S., Gill, J., Roth, M. & Gorlick, R., Sep 1 2015, ... Detection of circulating tumor DNA in patients with osteosarcoma. Barris, D. M., Weiner, S. B., Dubin, R. A., Fremed, M., Zhang ... Skp2 Depletion Reduces Tumor-Initiating Properties and Promotes Apoptosis in Synovial Sarcoma. Wang, J., Sato, K., ODonnell, E ...
This review will discuss the unique pancreatic tumor microenvironment, including the cells and receptors that transform the ... CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis ... CD8 Cytotoxic and CD4 helper T-cells or tumor infiltrating lymphocytes (TILs). The presence of TILs in pancreatic cancer has ... Tumor infiltrating lymphocytes (TILs), engineered T- cells that express a specific cancer T-cell receptor (TCR), and T- cells ...
How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to ... N2 - How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and ... AB - How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and ... abstract = "How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment ( ...
Leveraging and enhancing the power of tumor infiltrating lymphocytes (TIL) to treat, and potentially cure, all solid tumors. ...
DEGs with a prognostic value considered as candidate genes were evaluated, followed by genetic analysis of tumor infiltrating ... T cells were significantly higher than those in tumor cells, especially regulatory T cell infiltration was significantly ... increased in BM tumors. We analyzed gene expression signatures specifically associated with the development of bone metastases ... We sought to identify differentially expressed genes between patient-matched primary and bone metastatic CRPC tumors. ...
Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which ... Efficacy of Adoptive Therapy with Tumor-infiltrating Lymphocytes and Recombinant Interleukin-2 in Advanced Cutaneous Melanoma: ... Conclusions: Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI ... Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. ...
Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model.. Roth MD1, Harui ... The complex interactions that occur between human tumors, tumor infiltrating lymphocytes (TIL) and the systemic immune system ... To date, large animal tumor models have been used for studying spontaneously formed tumors in dogs and cats [11](Vail, 2000, ... Allografts of the outbred-canine transplanted venereal tumor have been used to test the ability to detect tumors using X-ray ...
Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion. Cancer Res. 2020 11 01; 80( ... B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor system in vitro. J Immunol. 1996 Jan 15; 156(2 ... Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of ... ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo. J ...
CD103+ tumour-infiltrating lymphocytes. Mechanistically, tumour αV regulates CD8 T cell recruitment, induces CD103 expression ... In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating ... T lymphocytes play an important role in antiviral defenses. However, T cell frequency and functionality may be affected during ... Integrin-αV-mediated activation of TGF-ß regulates anti-tumour CD8 T cell immunity and response to PD-1 blockade. ...
... enabling the development of next generation therapies for solid tumors. ... Processing and sequencing of patient tumor samples to identify tumor-infiltrating lymphocytes (TILs). ... Identification of novel shared T cell receptor targets of productive immune responses against solid tumors and other diseases. ... We combine high dimensional single cell sequencing data to identify TCRs responsible for anti tumor immune responses. ...
... are believed to be increasing tumor infiltrating lymphocytes that have been exhausted against the microenvironment of the tumor ... A novel study indicates that nicotinamide riboside is responsible for recharging tumor-infiltrating lymphocytes by acting on ... It was observed that the whole mechanism was driven by the stressors in the microenvironment of the tumor. In addition to this ...
We then carried out single cell TCRseq/RNAseq of tumor infiltrating T lymphocytes (TIL) to enumerate the genome wide digital ... We evaluated peripheral blood and tumor infiltrating lymphocytes from seven patients treated with nivolumab. To identify ... CI, confidence interval; HR, hazard ratio; IC, tumour-infiltrating immune cell; ITT, intention-to-treat; OS, overall survival; ... In vivo antitumor efficacy (n=30) was evaluated by median survival and tumor bioluminescence in mice bearing lung ADC tumors. ...
T cells and reverse anergy in tumor infiltrating AC-42 lymphocytes. If on-target, off-tumor or unforeseen toxicities are ... and FasL on tumor cells. More significantly, IL-12 has been shown to modulate the hostile tumor microenvironment through ... it may not be AC-42 sufficient in creating an effective CAR against a solid tumor given the inhibitory tumor AC-42 ... This will be the first time CAR T cells are injected intraperitoneally directly into the site of the tumor within the abdomen ...

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