MicroenvironmentLymphocytesImmunityProgressionDendritic cellsCytotoxicCarcinoembryonicMelanomaOccursMechanismsImmunotherapyInhibitorEndothelial cellsAssaysAngiogenesisEfficacyTherapiesCellularHeterogeneousResistancePopulationsMetastaticCancersInnateCytokinesMiceMediatesAdultsReceptorMethodsPreliminaryEliminationSurvivalPotentialRecognitionExpressionTherapeuticHuman
Microenvironment8
- While GB tumors are frequently infiltrated by natural killer (NK) cells, these are actively suppressed by the GB cells and the GB tumor microenvironment. (frontiersin.org)
- Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. (frontiersin.org)
- Nevertheless, the composition of the immunologic tumor microenvironment undergoes changes upon radiotherapy, chemotherapy, or even after anti-angiogenic therapy ( 6 ). (frontiersin.org)
- Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. (hindawi.com)
- Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy. (hindawi.com)
- However, the tumor microenvironment (TME) imposes different mechanisms that facilitate the impairment of DC functions, such as inefficient antigen presentation or polarization into immunosuppressive DCs. (mdpi.com)
- TIL exhibit tumor-specificity but are obviously impaired in their capacity to eradicate tumor targets in situ within the tumor microenvironment. (biomedcentral.com)
- Regardless of the therapeutic approach, the heterogeneity of pancreatic cancer cells and the complexity of its tumor microenvironment contribute to the emergence of drug resistance. (frontiersin.org)
Lymphocytes9
- As shown by multiplex tissue immunofluorescence and intravital microscopy, combined immunotherapy treatments enhance T cell infiltration and the intratumoral performance of T lymphocytes. (unav.edu)
- Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. (nwbio.com)
- In contrast to other cancers such as adenocarcinomas of the lung or melanoma, primary brain tumors like GB and low grade gliomas (LGG) are known as rather immunologically "cold" tumors, typically with low numbers of tumor-infiltrating lymphocytes (TILs) ( 4 ), and the mere amount of TILs is not associated with patient survival ( 5 ). (frontiersin.org)
- In the context of cancer, appropriately activated DCs can induce anti-tumor immunity by activating innate immune cells and tumor-specific lymphocytes that target cancer cells. (mdpi.com)
- The complex interactions that occur between human tumors, tumor infiltrating lymphocytes (TIL) and the systemic immune system are likely to define critical factors in the host response to cancer. (biomedcentral.com)
- The immune system in NOD/SCID/IL-2Rγnull (NSG) mice was reconstituted by the co-administration of human peripheral blood lymphocytes (PBL) or subsets (CD4+ or CD8+) and autologous human dendritic cells (DC), and animals simultaneously challenged by implanting human prostate cancer cells (PC3 line). (biomedcentral.com)
- Tumor infiltrating lymphocytes (TIL) are a universal feature of human cancers and may hold an important key to unlocking effective cancer immunotherapy [ 1 - 3 ]. (biomedcentral.com)
- As a proof of concept, peripheral blood lymphocytes (PBL) and dendritic cells (DC) were obtained from healthy donors and used to reconstitute NSG animals, followed by implantation with cells from the human prostate cancer cell line, PC3. (biomedcentral.com)
- Indeed, an increase in the recruitment of cytotoxic CD8 + T-lymphocytes into the tumor is mediated by chemokines such as C-C motif chemokine ligand 5, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 and is correlated to lower metastasis risk and better outcome for patients [ 1 - 3 ] [Figure 1] . (oaepublish.com)
Immunity4
- Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. (hindawi.com)
- This humanized platform provides an opportunity to study the two-way interaction that occurs between human immunity and tumor growth, over time, and to manipulate individual components to test hypotheses and potential clinical impact. (biomedcentral.com)
- Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. (biomedcentral.com)
- The new incoming challenge is now therefore to overcome these resistance and new recent data presented epigenetic modifications as promising targets to restore anti-tumor immunity. (oaepublish.com)
Progression4
- This upregulation was correlated with tumor progression. (molvis.org)
- Angiogenesis, the growth of new blood vessels, occurs at different stages during embryonic development, physiological processes such as wound healing and reproduction, and numerous diseases, including inflammation, tumor progression, and metastasis [ 1 ]. (hindawi.com)
- Importantly, during tumor progression, myeloid cells are implicated in promoting tumor angiogenesis, causing resistance against antiangiogenic therapies in cancer, and suppressing the immune response during cancer [ 3 - 5 ]. (hindawi.com)
- Cell surface glycoprotein that plays a role in cell adhesion and tumor progression. (cusabio.cn)
Dendritic cells11
- Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. (nwbio.com)
- Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. (nwbio.com)
- Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. (nwbio.com)
- Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study. (nwbio.com)
- Babatz J, Röllig C, Löbel B, Folprecht G, Haack M, Günther H, Köhne CH, Ehninger G, Schmitz M, Bornhäuser M. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. (nwbio.com)
- Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, Blanck JP, Johnston DA, Palucka AK, Fay J. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon. (nwbio.com)
- Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. (nwbio.com)
- Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA. (nwbio.com)
- Bleumer I, Tiemessen DM, Oosterwijk-Wakka JC, Völler MC, De Weijer K, Mulders PF, Oosterwijk E. Preliminary analysis of patients with progressive renal cell carcinoma vaccinated with CA9-peptide-pulsed mature dendritic cells. (nwbio.com)
- NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. (frontiersin.org)
- Dendritic cells (DCs) are specialized antigen-presenting cells that have a notable role in the initiation and regulation of innate and adaptive immune responses. (mdpi.com)
Cytotoxic1
- These therapeutic methods, including but not limited to oncolytic virus therapies, T-cell therapies and cancer vaccines, are based on the body's ability to recognize mutated antigen peptides presented on the cell surface by MCH-receptors (also known as HLA-receptors in humans) and the disposal of the malignant cells by cytotoxic T-cells. (helsinki.fi)
Carcinoembryonic1
- Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM5 and CEACAM8. (cusabio.cn)
Melanoma1
- Choroidal melanoma is the most common primary malignant ocular tumor in human adults. (molvis.org)
Occurs1
- In 1971, Dr. Judah Folkman observed that neovascularization occurs around tumors and proposed that new blood vessel growth is necessary to supply nutrients and oxygen to tumor cells during exponential tumor growth [ 6 ]. (hindawi.com)
Mechanisms6
- Additionally, induced co -expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. (unav.edu)
- This offers significant advantages for studying tumor pathogenesis and molecular mechanisms of oncogenesis caused by a single initiating oncogenic event introduced through the mouse germ line. (molvis.org)
- These observations stimulated an intensive search for the mechanisms regulating tumor angiogenesis. (hindawi.com)
- While a basic understanding of the composition and phenotype of TIL has come from the study of human tumors, these studies are limited by patient heterogeneity, a lack of access to corresponding lymphoid tissue, and an inability to directly investigate mechanisms and interactions. (biomedcentral.com)
- Moreover, single-cell sequencing provides unique insights into the mechanisms of pancreatic cancer metastasis and cachexia, paving the way for developing novel preventive strategies. (frontiersin.org)
- It unlocks novel dimensions by uncovering elusive cell populations and tumor heterogeneities for early detection, unraveling mechanisms of treatment resistance, tailoring therapies to individuals, and illuminating metastasis and cachexia pathways, thereby opening fresh avenues for preventive strategies. (frontiersin.org)
Immunotherapy4
- Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience. (nwbio.com)
- Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo . (frontiersin.org)
- We then outline preclinical approaches that employ CAR-NK cells for GB immunotherapy, and give an overview on the ongoing clinical development of ErbB2 (HER2)-specific CAR-NK cells currently applied in a phase I clinical trial in glioblastoma patients. (frontiersin.org)
- Immunotherapy protocols are designed to annihilate immune escape in cancer cells and restore elimination of cancer cells. (oaepublish.com)
Inhibitor1
- Indeed, both DNA methylation and post-translational histone modifications have been described to regulate immune checkpoint inhibitor expression, tumor-associated antigen presentation or cancer cell editing by the immune system and therefore establishing epigenetic drugs as a potential complement to immunotherapies to improve their efficiency. (oaepublish.com)
Endothelial cells6
- It is now known that new blood vessels originate from preexisting vessels by activation, proliferation and migration of endothelial cells through a process named "angiogenesis" [ 4 ]. (hindawi.com)
- Specific growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), stimulate the proliferation and migration of naturally quiescent endothelial cells, resulting in the formation of new vessel structures during embryonic development and tumor growth [ 7 ]. (hindawi.com)
- Vasculogenesis is the coalescence of new blood vessels from individual endothelial cells or progenitor cells. (hindawi.com)
- This suggested that EPCs are able to differentiate into endothelial cells and that such cells are incorporated into sites of active angiogenesis including ischemia, tumor angiogenesis, and metastasis in adult organisms [ 16 , 17 ]. (hindawi.com)
- Plays a role in neutrophil adhesion to cytokine-activated endothelial cells. (cusabio.cn)
- positively regulates cell migration, cell adhesion to endothelial cells and cell invasion. (cusabio.cn)
Assays1
- 2. Interferon γ cytokine secretion was determined by ELISPOT to assess PBMC response against known antigens in a preliminary experiment to approximate usable range for the following antigen specific PBMC assays. (helsinki.fi)
Angiogenesis3
- In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. (hindawi.com)
- Although tumor cells were first thought to drive the cellular events underpinning tumor angiogenesis and growth, considerable evidence has now emerged for the central role of tumor infiltrating myeloid cells such as monocytes, macrophages, and neutrophils in this phenomenon [ 8 - 12 ]. (hindawi.com)
- So, immune escape has now been included as one of the new hallmarks of cancer development described in the revised version of Hanahan and Weinberg [ 5 ] in 2011, together with resistance to cell death, replicative immortality or induced angiogenesis, for example. (oaepublish.com)
Efficacy3
- Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. (unav.edu)
- Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
- Rapid clearance and reduced cell entry thus lead to decreased amount of oncolytic adenovirus in target cells and decreased efficacy. (helsinki.fi)
Therapies2
- Even though the idea of an immune system actively searching for and disposing of potential mutated tumor cells is over a century old, only recent developments in various fields such as mass spectrometry, immuno-checkpoint blockade strategies and in silico modelling have enabled the realization of the full potential of recruiting immune system to fight cancer and the possibilities of personalized therapies. (helsinki.fi)
- While conventional animal models have identified an array of potential anti-tumor therapies, mouse models often fail to translate into effective human treatments. (biomedcentral.com)
Cellular1
- Single-cell sequencing is a high-throughput technique that enables detection of genomic, transcriptomic, and epigenomic information at the individual cell level, offering significant advantages in detecting cellular heterogeneity, precise cell classification, and identifying rare subpopulations. (frontiersin.org)
Heterogeneous2
- Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. (hindawi.com)
- During the Elimination phase, some newly transformed cells can be quickly eliminated by immune effector cells, such as natural killers (NKs), but this phase can also favor the development of heterogeneous tumor cancer cells resulting in the selection of new variants resistant to immune edition. (oaepublish.com)
Resistance2
- Also involved in the metastatic cascade process by inducing gain resistance to anoikis of pancreatic adenocarcinoma and colorectal carcinoma cells. (cusabio.cn)
- Further growth of cancer cells selected during the Equilibrium phase may then lead to the acquisition of aggressive phenotypes and resistance to immune system elimination inducing clinical lesions. (oaepublish.com)
Populations1
- Transcriptomic profiling of T-cell populations in non-muscle invasive and muscle invasive bladder cancer. (lu.se)
Metastatic1
- Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. (nwbio.com)
Cancers3
- The role of two members of the ETS (E26 avian leukemia oncogene) family of transcription factors, ETS-1 and ETS-2, has been investigated in many cancers but has not yet been studied in ocular tumors. (molvis.org)
- With the advancements in prostate-specific antigen (PSA) screening, most prostate cancers are detected at the regional stages (clinically localised disease). (biomedcentral.com)
- However, although these new therapeutic strategies, which are designed to limit immune escape of cancer cells, have been used or tested successfully in many different cancers, a large proportion of patients have been described to resist and not respond to these new treatments. (oaepublish.com)
Innate1
- The innate immune system is mainly composed of myeloid lineage cells, such as macrophages, neutrophils, and mast cells [ 2 ]. (hindawi.com)
Cytokines1
- Human cytokines were readily detectible in the serum and exhibited a different profile in animals implanted with PBL alone, tumor alone, and those reconstituted with both. (biomedcentral.com)
Mice2
- We show that treatment of the mice with a combination of anti-CTLA-4 + anti-PD1 mAbs results in partial clearance of the tumor with an improvement in survival. (unav.edu)
- Unlike cancer arising in the human population, tumors in genetically engineered mouse models arise in mice with well defined genetic backgrounds where genetic variability can be minimized. (molvis.org)
Mediates1
- CD137 (4-1BB) is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). (unav.edu)
Adults2
- Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults and currently incurable. (frontiersin.org)
- Glioblastoma (GB) is the most frequent malignant primary brain tumor in adults, without any curative treatment options available at present. (frontiersin.org)
Receptor3
- Another challenge is the cell entry of oncolytic adenovirus, which is mainly mediated by the Coxsackie-Adenovirus receptor and this receptor is downregulated in various cancer cells. (helsinki.fi)
- Upon culture in endothelial growth media, these cells expressed endothelial lineage markers, such as CD31, Tie2, and VEGF receptor 2 (VEGFR2), and incorporated into blood vessels in ischemic tissues. (hindawi.com)
- Antigen presentation by the professional antigen-presenting cells (APCs) are normally recognized by immune cells via a surface T-cell receptor (TCR), leading to the induction of naive CD8 + T-cell clonal expansion and differentiation and finally resulting in the cell death of APCs. (oaepublish.com)
Methods1
- In silico methods were successfully used to characterize previously identified HLA-restricted peptides and one previously identified immunogenic T-cell epitope. (helsinki.fi)
Preliminary1
- Preliminary MTS assay is used to determine linear range and optimal time frame for the PBMC/cancer cell co-culture killing assay. (helsinki.fi)
Elimination2
- The immune system plays a key role in surveillance against cancer, but some tumour cells evolve to escape immune elimination [ 4 ]. (biomedcentral.com)
- Specific tumor-associated antigens (TAAs) expressed by cancer cells can be identified by the immune system and results in the activation of immune system effectors and the consequent elimination of the cancer cells. (oaepublish.com)
Survival1
- Mammalian cells require oxygen and nutrients for their survival and are therefore located within 100 to 200 m of blood vessels, the diffusion limit of oxygen. (hindawi.com)
Potential1
- Overall, single-cell sequencing has immense potential in promoting early diagnosis, guiding personalized treatment, and preventing complications of pancreatic cancer. (frontiersin.org)
Recognition1
- Examples of direct implication of epigenetic modifications in immune recognition of cancer cells. (oaepublish.com)
Expression5
- The directed expression of SV40 T antigen has led to the development of several important transgenic models with spontaneous epithelial tumor formation. (molvis.org)
- Flow cytometric analysis provided essential information of the cell line HLA-1 expression. (helsinki.fi)
- Additional information of PD-L1 expression can be used to evaluate cell line's immune-evasion abilities. (helsinki.fi)
- 13 ] isolated mononuclear cells from human peripheral blood that were enriched for expression of the hematopoietic stem cell marker CD34 [ 13 ]. (hindawi.com)
- These TIL exhibited a unique phenotype when compared to splenocytes with a predominance of CD8+ T cells that exhibited increased expression of CD69, CD56, and an effector memory phenotype. (biomedcentral.com)
Therapeutic1
- Upon mRNA intratumoral injections in the transplantable mouse cancer models CT26, MC38, and B16OVA, potent therapeutic effects were observed following repeated injections into the tumors. (unav.edu)
Human3
- A tumor-bearing huPBL-NSG model was established in which human leukocytes reconstituted secondary lymphoid organs and promoted the accumulation of TIL. (biomedcentral.com)
- Simultaneous implantation of human PBL, DC and tumor results in a huPBL-NSG model that recapitulates the development of human TIL and allows an assessment of tumor and immune system interaction that cannot be carried out in humans. (biomedcentral.com)
- The work presented in this study carries animal modeling one step further by simultaneously humanizing the immune system of recipient NOD/SCID/IL-2Rγnull (NSG) animals and challenging them with implanted human tumor cells. (biomedcentral.com)