The last fifteen years have seen a reemergence of interest in cancer immunosurveillance and a broadening of this concept into one termed cancer immunoediting. The latter, supported by strong experimental data derived from murine tumor models and provocative correlative data obtained by studying huma …

Cancer immunology is an interdisciplinary branch of biology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer. Cancer immunology is an interdisciplinary branch of biology concerned with the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, where the immune system is used to treat cancer. Cancer immunosurveillance is a theory formulated in 1957 by Burnet and Thomas, who proposed that lymphocytes act as sentinels in recognizing and eliminating continuously arising, nascent transformed cells. Cancer immunosurveillance appears to be an important host ...

The resurgent theory of cancer immunosurveillance holds that the immune system plays an important role in the suppression of tumors, particularly in the elimination of early neoplastic lesions. Tumors with reduced immunogenicity or those that have acquired mechanisms to suppress immune effector func …

Objective. Balancing immunosuppression to prevent rejection while minimizing infection/drug toxicity risk is a challenge in organ transplantation. Drug monitoring alone or with functional monitoring is inadequate to measure the immune response after transplantation. The Food and Drug Administration (FDA)-approved immune monitoring assay, ImmuKnow, offers an noninvasive method to assess the immune status of transplanted patients by measuring adenosine triphosphate (ATP) released from CD4 T cells. Herein, we have evaluated ATP levels reflecting the immune responses of Chinese kidney transplant recipients as a monitoring parameter to guide treatment after transplantation. Methods. From October 2008 to March 2010, we recruited 259 kidney transplant patients who were divided into four groups: stable (n = 174), postoperative infection (n = 32), postoperative rejection (n = 16), and high-dose corticosteroid treatment (n = 33). The ImmuKnow assay was performed to measure CD4 T-cell ATP levels. No ...

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. Immunomodulators and biologic agents (hereafter referred to jointly as immunosuppression) are effective in treating IBD and recent evidence supports their introduction earlier in the disease course.1 ,2 An important concern to both patients and physicians considering immunosuppression for the treatment of IBD is the potential associated cancer risk.. It is estimated that 1.6 million new diagnoses of cancer will be made in 2013 among the general population in the USA alone.3 Likewise, as the population of patients with IBD ages, it is inevitable that some will develop cancer. As such, in addition to concerns about the development of de novo cancer in a patient without a history of cancer, clinicians caring for patients with IBD are increasingly challenged with questions about IBD management after the development of cancer. Conversely, oncologists are often concerned about how to manage IBD in ...

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TY - JOUR. T1 - Cancer and mTOR inhibitors in kidney transplantation recipients. AU - Kao, Chih Chin. AU - Liu, Jia Sin. AU - Chang, Yu Kang. AU - Lin, Ming Huang. AU - Lin, Yen Chung. AU - Chen, Hsi Hsien. AU - Chang, Wei Chiao. AU - Hsu, Chih Cheng. AU - Wu, Mai Szu. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Background: Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods: In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results: Patients were divided into two groups: mTOR inhibitors users (study group, ...

Transforming growth factor-β (TGF-β) suppresses innate and adaptive immune responses via multiple mechanisms. TGF-β also importantly contributes to the formation of an immunosuppressive tumor microenvironment thereby promoting tumor growth. Amongst others, TGF-β impairs tumor recognition by cytotoxic lymphocytes via NKG2D. NKG2D is a homodimeric C-type lectin-like receptor expressed on virtually all human NK cells and cytotoxic T cells, and stimulates their effector functions upon engagement by NKG2D ligands (NKG2DL). While NKG2DL are mostly absent from healthy cells, their expression is induced by cellular stress and malignant transformation, and, accordingly, frequently detected on various tumor cells. Hence, the NKG2D axis is thought to play a decisive role in cancer immunosurveillance and, obviously, often is compromised in clinically apparent tumors. There is mounting evidence that TGF-β, produced by tumor cells and immune cells in the tumor microenvironment, plays a key role in blunting the

Immune system is composed of innate and adaptive responses and plays critical roles in cancer development and destruction. A century ago, Paul Ehrlich postulated that cancer would be quite common in long-lived organisms if not for the protective effects of immunity. About 50 years later, Burnet and Thomas proposed the concept of cancer immunosurveillance based on the experimental evidence of immune recognition of tumor antigens expressed on tumor cells (Dunn et al. 2004 ) . In 1971, the US Congress created a National Cancer Act - a War on Cancer. ...

Dr. Emmanuel Katsanis, MD, and his laboratory conduct basic and translational research aimed at advancing new cancer immunotherapeutic strategies. His expertise is in stem cell transplant immunology, cellular therapy, and cancer vaccine approaches.Immunity against tumors depends on complex innate and adaptive immune responses that involve the sequential mobilization of messenger and killer immune cells. However, despite the arsenal harbored by the immune system to ensure tumor immunosurveillance, cancers can escape immune detection and elimination. Current research in the laboratory is evaluating immuno- and chemo-immunotherapeutic strategies to promote anti-tumor immune responses following bone marrow transplantation, while investigating approaches to mitigate graft versus host effects ...

Immune reactions against melanomas occur spontaneously and this is called regression. Thus, melanoma is considered a useful model disease for cancer immuno-therapy, but the consecutive steps that initiate spontaneous melanoma regression are not characterized. Mast cells (MC) are considered potent immune modulators with both pro-inflammatory and regulatory function. We found the most prominent MC infiltrates in melanomas with spontaneous immune regression. Moreover, MC deficient KitW-sh and KitW/KitW-v mice showed accelerated melanoma growth compared to wildtype that could be reverted by MC reconstitution. In addition, activation of MC could compensate for dendritic cell (DC) activation indicating productive crosstalk between MC and DC underlying MC mediated induction of anti-tumor immunity. Therefore, MC mediated tumor immunosurveillance will be analyzed including the characterization of consequences on T cell immunity in vitro and in vivo during melanoma growth using the appropriate knock-out ...

Immune reactions against melanomas occur spontaneously and this is called regression. Thus, melanoma is considered a useful model disease for cancer immuno-therapy, but the consecutive steps that initiate spontaneous melanoma regression are not characterized. Mast cells (MC) are considered potent immune modulators with both pro-inflammatory and regulatory function. We found the most prominent MC infiltrates in melanomas with spontaneous immune regression. Moreover, MC deficient KitW-sh and KitW/KitW-v mice showed accelerated melanoma growth compared to wildtype that could be reverted by MC reconstitution. In addition, activation of MC could compensate for dendritic cell (DC) activation indicating productive crosstalk between MC and DC underlying MC mediated induction of anti-tumor immunity. Therefore, MC mediated tumor immunosurveillance will be analyzed including the characterization of consequences on T cell immunity in vitro and in vivo during melanoma growth using the appropriate knock-out ...

CCL21, CCL25, CXCL13) are constitutively expressed and control physiologic trafficking of cells of the adoptive immune system during hematopoiesis and immunosurveillance ...

Murine Qa‐2 and human leukocyte antigen (HLA)‐G are young MHC Ib proteins in that they diverged from MHC Ia less than 20 million years ago, and therefore have many similarities with the classical Ia molecules: they present a repertoire of nonameric peptides, contain a CD8 binding loop, associate with β2‐microglobulin (β2m), display similar exon-intron organization and even share a high degree of amino‐acid sequence homology (Seliger et al, 2003).. The murine Qa‐2 region, located in the H2‐Q class Ib locus, encodes the proteins Q8 and Q9 in C57BL/6 (B6) mice, which differ from each other by 20 amino acids located in the α1 and α2 domains. These proteins have overlapping peptide‐binding motifs and are recognized by cross‐reactive anti‐tumour CTLs, and therefore appear to be functionally equivalent (Chiang & Stroynowski, 2006). Surface expression of Qa‐2 molecules requires a functional TAP (transporter associated with antigen processing) peptide transporter (Tabaczewski et ...

The theory of cancer immunoediting, which describes the dynamic interactions between tumors and host immune cells that shape the character of each compartment, is foundational for understanding cancer immunotherapy. Few models exist that facilitate in-depth study of each of the three canonical phases of immunoediting: elimination, equilibrium, and escape. Here, we utilized NPK-C1, a transplantable prostate tumor model that we found recapitulated the three phases of immunoediting spontaneously in immunocompetent animals. Given that a significant portion of NPK-C1 tumors reliably progressed to the escape phase, we were able to delineate cell types and mechanisms differentially prevalent in equilibrium versus escape phases. Using high-dimensional flow cytometry, we found that activated CD4+ effector T cells were enriched in regressing tumors, highlighting a role for CD4+ T cells in antitumor immunity. CD8+ T cells were also important for NPK-C1 control, specifically, central memory-like cytotoxic ...

Cytotoxic lymphocytes genetically modified to express so-called chimeric antigen receptors (CARs) hold promise for adoptive cancer immunotherapy. CARs are artificial transmembrane proteins that typically contain an extracellular single-chain antibody fragment (scFv) for recognition of antigens on the tumor cell surface, fused to intracellular signaling moieties such as CD3zeta (first generation CAR), or composite sequences harboring in addition one or more costimulatory protein domains (second and third generation CARs). While potent antitumoral activity of CAR-modified T cells has been demonstrated in patients with hematological malignancies, experience with CAR-engineered natural killer (NK) cells and their clinical development is still limited. NK cells play a crucial role in cancer immunosurveillance and represent an important effector cell type for adoptive cancer immunotherapy. Unlike T cells, they do not require prior sensitization and recognition of peptide antigens presented in complex ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells transdifferentiate into highly motile, invasive, mesenchymal-like cells, giving rise to disseminating tumor cells. Few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment were shown to drive EMT, but few studies investigated the consequences of EMT for tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to natural killer (NK) cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without affecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in 2 lung and 1 breast adenocarcinoma patient cohorts and decreased metastasis. Our observations reveal a novel ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

During epithelial-mesenchymal transition (EMT) epithelial cancer cells trans-differentiate into highly-motile, invasive, mesenchymal-like cells giving rise to disseminating tumor cells. Only few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment was shown to drive EMT, but few studies investigated the consequences of EMT on tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to NK cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without effecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in two lung and one breast adenocarcinoma patient cohorts and decreased metastasis. Our observation reveal a novel NK-mediated, ...

Implementation of immunotherapy in breast cancer management requires optimisation of current regimens and identification of biomarkers

Implementation of immunotherapy in breast cancer management requires optimisation of current regimens and identification of biomarkers

Immunoediting is a dynamic process that consists of immunosurveillance and tumor progression. It describes the relation between the tumor cells and the immune system. It is made up of three phases: elimination, equilibrium, and escape. Immunoediting is characterized by changes in the immunogenicity of tumors due to the anti-tumor response of the immune system, resulting in the emergence of immune-resistant variants. The elimination phase, also known as immunosurveillance, includes innate and adaptive immune responses to tumour cells. For the innate immune response, several effector cells such as natural killer cells and T cells are activated by the inflammatory cytokines, which are released by the growing tumour cells, macrophages and stromal cells surrounding the tumour cells. The recruited tumour-infiltrating NK cells and macrophages produce interleukin 12 and interferon gamma, which kill tumour cells by cytotoxic mechanisms such as perforin, TNF-related apoptosis-inducing ligands (TRAILs), ...

Tumour infiltrating lymphocytes have been associated to a better prognosis in colorectal cancers. Microsatellite unstable tumours present a greater infiltration by these ..

She read several books today - including Mouse Soup, and Wild About Books. I had her read a chapter of our book to herself when I got home and report to me what she read. That is a skill she needs to develop to read books by herself. Mark and her rode bikes outside. They did some more of our workbooks for math, G&T English and Reading Comprehension. When I was home we watched the Earth documentary Grandma had Netflixed and enjoyed it quite a bit ...

TY - CHAP. T1 - From cancer immunoediting to new strategies in cancer immunotherapy. T2 - The roles of immune cells and mechanics in oncology. AU - Aragon-Sanabria, Virginia. AU - Kim, Gloria B.. AU - Dong, Cheng. PY - 2018/1/1. Y1 - 2018/1/1. N2 - For the last three decades, the concept of immunoediting has evolved to characterize our increasing understanding of the interactions between cells from the immune system and cancer development. Elucidating the role of immune cells in the progression of cancer has been very challenging due to their dual role; the immune system can either suppress tumor formation by killing cancer cells, or it can also promote tumor growth. Revealing how immune cells are hampered by the tumor microenvironment and how they aid tumor progression has signaled strategies to reverse these effects and control cancer cell growth; this has been the advent of immunotherapy design. More recently, the role of physical forces in the process of immunoediting has been highlighted by ...

Dietary restriction (DR) was shown to impact on tumor growth with very variable effects depending on the cancer type. However, how DR limits cancer progression remains largely unknown. Here, we demonstrate that feeding mice a low-protein (Low PROT) isocaloric diet but not a low-carbohydrate (Low CHO) diet reduced tumor growth in three independent mouse cancer models. Surprisingly, this effect relies on anticancer immunosurveillance, as depleting CD8 T cells, antigen-presenting cells (APCs), or using immunodeficient mice prevented the beneficial effect of the diet. Mechanistically, we established that a Low PROT diet induces the unfolded protein response (UPR) in tumor cells through the activation of IRE1α and RIG1 signaling, thereby resulting in cytokine production and mounting an efficient anticancer immune response. Collectively, our data suggest that a Low PROT diet induces an IRE1α-dependent UPR in cancer cells, enhancing a CD8-mediated T cell response against tumors.

The theory of cancer immunoediting refers to mechanisms by which the immune system can suppress or promote tumour progression. and that Usp18 is normally a story inhibitor of interferon- signalling. Knockdown of the interferon- particular receptor subunit IL-28R1 in Usp18 lacking MECs significantly enhances tumor development. Used jointly, our data recommend that concentrating on Usp18 may end up being a practical strategy to increase antitumour defenses while controlling the protumour activity of the resistant program. growth assay upon recovery of Usp18 insufficiency (Fig 2) recommending that absence of Usp18 will not really have got an inbuilt impact on growth of PyVmT MECs. Next, we attended to if the price of apoptosis was changed in Usp18 lacking cells. Neither amount of TUNEL-positive PyVmT/Usp18 KO tumor cells (Fig 2), nor the percentage of AnnexinV-positive stably transduced PyVmT/Usp18 KO MECs (Fig 2) was considerably different from settings, recommending that the noticed decrease in ...

Natural Killer (NK) cells contribute to the control of cancer through immunosurveillance and may influence phenotypic sculpting of cancer through immunoediting. NK cells may also contribute to the control of hematological malignancies such as acute myeloid leukemia (AML) following allogeneic stem cell transplantation. However, no studies have shown direct clinical evidence that supports immunoediting by NK cells in AML at presentation, or whether activating ligand expression at diagnosis serves as a prognostic indicator of survival. We now show that at diagnosis, expression of NK cell ligands on AML blast populations is heterogeneous. Furthermore, expression of multiple activating ligands is associated with favorable cytogenetics and improved leukemia-free survival. In analyses of paired diagnostic and relapse samples, AML blasts exhibiting lower expression of activating ligands were selectively increased at relapse, indicating that NK cell-mediated blast immunoediting occurred prior to AML ...

Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations. Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts. We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Kras-mut/TP53-mut colorectal cancer cells the 15 kDa βGBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a

Cancer immunoediting describes the mechanisms by which the immune system responds to cancer and can be broadly split into three phases: elimination, equilibrium, and escape. During the elimination phase, the immune system surveils and eliminates tumor cells through the production of inflammatory cytokines, recognition of tumor antigens by dendritic cells, or activation of natural killer cells. Equilibrium describes a phase of cancer persistence in which there is a selection for tumor cells that were not eliminated. During this phase, tumor cells are selected through immune cell exhaustion or inhibition, genetic and epigenetic changes, or resistance to immune detection. Escape occurs when tumors cells have escaped immune detection and are able to grow and expand. This can happen through a variety of mechanisms including the shedding of tumor recognition antigens, MDSC-induced immunosuppression, or development of a microenvironment that supports T cell apoptosis.. Click on the poster below to view ...

TY - JOUR. T1 - Immune functional assay for immunosuppressive management in post-transplant malignancy. AU - Uemura, Tadahiro. AU - Riley III, Thomas. AU - Khan, Akhtar. AU - Hollenbeak, Christopher S.. AU - Schreibman, Ian. AU - Ghahramani, Nasrollah. AU - Reeves, Brian. AU - Domen, Ronald. AU - Zander, Dani S.. AU - Kadry, Zakiyah. PY - 2011/1/1. Y1 - 2011/1/1. N2 - Immunosuppression management in post-transplant malignancy is challenging because of a lack of objective immunologic assessment tools. The ImmuKnow assay measures the ATP level from CD4 T cells, quantifying cell-mediated immunity and providing an insight into the immune status of transplant recipients. Its potential use in patients with post-transplant de novo malignancy was evaluated. Thirteen adult transplant patients with de novo malignancy were divided into survivors (n=9) and non-survivors (n=4) after malignancy treatment. Tacrolimus and the ImmuKnow levels were monitored before, during, and after malignancy treatment. The ...

T cells are uniquely gifted immune cells capable of trafficking anywhere in the body and recognizing their target cells with exquisite specificity. They can interact with any given cell as long as it expresses the right antigen. However, we do not know what the final outcome of a given T cell-target cell interaction is for every single cell in our bodies. We do know, however, that some cells such as cancer cells can escape T cell killing while some other cell types are more prone to autoimmunity (e.g. pancreatic beta cells). What are the mechanisms behind these differences? To address this question, we recently generated a new technology called the Jedi mouse (Agudo, Nat. Biotech., 2015). Jedi T cells recognize GFP as their cognate antigen and therefore, can be used in combination with any of the available GFP-expressing mouse lines, cells lines or microorganisms. In the Agudo lab, we are interested in using this platform to study immune surveillance of adult stem cells, cancer stem cells and ...

The skin represents the outermost defense against microbial and environmental insults. The importance of cutaneous integrity is emphasized by the multitude of strategies that counteract pathogen invasion, including the physical barrier provided by keratinocytes, the production of antimicrobial mediators by skin-resident cells, and the localization of immune cells in the different layers of the skin. It has become increasingly clear that epidermis and dermis do not merely represent anatomically distinct compartments, but rather directly and specifically shape the immune milieu to support the activities of resident leukocytes. In this study, we have identified an abundant population of resident dermal γδ T cells that displays a unique phenotypic profile, survival requirements, and migratory behavior as compared with its epidermal and systemic counterparts. Our results thus expand on the concept of microcompartmental specialization of distinct immune cell subsets within the skin. They further ...

NK cells have important functions in cancer immunosurveillance, bone marrow allograft rejection, fighting infections, tissue homeostasis and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or upregulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKR), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP3-generation by PI3K, and generation of diacylglycerol and IP3 by PLCγ. Here, we identify a novel role for the phosphorylated IP3 metabolite inositol(1,3,4,5)tetrakisphosphate (IP4) in NK cells. IP4 promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in ...

Vγ9Vδ2-T cells are considered as potent effector cells for tumor immunotherapy through directly killing tumor cells and indirectly regulating other innate and adaptive immune cells to establish anti-tumoral immunity. The anti-tumoral activity of Vγ9Vδ2-T cells is governed by a complicated set of activating and inhibitory cell receptors. In addition, cytokine milieu in tumor microenvironment can also induce the pro-tumoral activities and functional plasticity of Vγ9Vδ2-T cells. Here, we review the anti- versus pro-tumoral activities of Vγ9Vδ2-T cells, and discuss the mechanisms underlying the recognition, activation, differentiation and regulation of Vγ9Vδ2-T cells in tumor immunosurveillance. The comprehensive understanding the dual face of Vγ9Vδ2-T cells in tumor immunology may improve the therapeutic efficacy and clinical outcomes of Vγ9Vδ2-T cell-based tumor immunotherapy.

TY - JOUR. T1 - Immune functional assay for immunosuppressive management in post-transplant malignancy. AU - Uemura, Tadahiro. AU - Riley, Thomas R.. AU - Khan, Akhtar. AU - Hollenbeak, Christopher. AU - Schreibman, Ian. AU - Ghahramani, Nasrollah. AU - Reeves, Brian. AU - Domen, Ronald E.. AU - Zander, Dani S.. AU - Kadry, Zakiyah. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2011/1. Y1 - 2011/1. N2 - Immunosuppression management in post-transplant malignancy is challenging because of a lack of objective immunologic assessment tools. The ImmuKnow assay measures the ATP level from CD4 T cells, quantifying cell-mediated immunity and providing an insight into the immune status of transplant recipients. Its potential use in patients with post-transplant de novo malignancy was evaluated. Thirteen adult transplant patients with de novo malignancy were divided into survivors (n=9) and non-survivors (n=4) after malignancy treatment. Tacrolimus and the ImmuKnow levels were ...

TY - JOUR. T1 - Characterization of NKR+ T-cell subsets in human bone marrow. T2 - implications for immunosurveillance of neoplasia. AU - Dean, J. AU - McCarthy, D. AU - Doherty, D G. AU - OFarrelly, C. AU - Golden-Mason, L. AU - Lawler, Mark. PY - 2005/1. Y1 - 2005/1. N2 - In addition to hematopoietic progenitors, human bone marrow contains mature T/NK lymphocytes. Valpha24Vbeta11 NKT-cells, a subset of NK receptor+ (NKR+) T-cells in humans, are rare in bone marrow, suggesting the presence of other NKR+ T-cells which may contribute to tumor surveillance. NKR+/- T-cells were examined in blood (PB), and bone marrow from donors (DM) and patients with active hematopoietic malignancy (PM), or in remission (PR). T-cells in PR & PM were enriched for CD56+ and CD57+ subsets, compared to DM. All marrow NKR+/- T-cell subsets were more activated than PB. PM and, surprisingly, PR marrow contained more activated cells than DM. CD8+ cells were significantly increased in all patient marrows and there was ...

Otte, Jean-Bernard ; Yandza, T ; Tan, K C ; Salizzoni, M. ; de Ville de Goyet, J ; et. al. Recent developments in pediatric liver transplantation.. In: Transplantation proceedings, Vol. 19, no. 5, p. 4361-4 (1987 ...

Ng VL, Mazariegos GV, Kelly B, Horslen S, McDiarmid SV, Magee JC, Loomes KM, Fischer RT, Sundaram SS, Lai JC, Te HS, Bucuvalas JC. Barriers to ideal outcomes after pediatric liver transplantation. Pediatr Transplant. 2019 09; 23(6):e13537 ...

Champalimaud Foundation This research, conducted at the Champalimaud Foundation in Lisbon, is focused on the immune response after implantation of human cancer cells in zebrafish. The cells in the implanted tumors were characterized using SORT-seq. Here, we explain how SORT-seq contributed to this remarkable study. Continue reading Cancer immunoediting is a process where the immune…. ...

Lifelong, nonspecific immunosuppressive drugs, although essential to preventing allograft rejection, impose a substantial risk of morbidity and mortality and hinder tumor immunosurveillance.52-55 Given the immune-regulatory properties of MSCs, these cells have been administered to transplant recipients with the hope of tipping the balance between effector and regulatory pathways and eventually promoting the host potential to control the immune response to the allograft without the use or with minimal use of immunosuppressive drugs. To date, this possibility has mainly been explored in kidney transplantation.7 Results from MSC-based therapy in kidney transplant recipients are, however, available from only six phase 1 clinical studies (four using autologous56-60 and two using allogeneic MSCs61,62) (Table 1), all with cells prepared by academic laboratories. Twelve studies in kidney transplant recipients are still ongoing, with no outcomes publicly available yet (Table 2).. In 2011, we first ...

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The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as hyperploid cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...

The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as hyperploid cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...

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Chemokines, Mouse, Calcium, Cell, Chemoattractants, Thyroid, Patients, Serum, Autoimmune Thyroiditis, Disease, T Cells, Human, Mice, Antigens, and Immunosurveillance

Luminex 200 set the standard for multiplexing, with over 11,000 units sold globally and more than fifty 510(k)-cleared assays available.