Checkpoint blockade blockade antigen of tumor. Medical search. Frequent questions

Breakthroughs in anti-tumor immunity have led to unprecedented advances in immunotherapy, yet it is now clear that the tumor microenvironment (TME) restrains immunity. (elifesciences.org)
As T cell metabolism dictates effector function, it is now apparent that the effect of cancer cell metabolism on the tumor microenvironment (TME) may impair anti-tumor immunity, and these new hallmarks of cancer are therefore inextricably linked. (elifesciences.org)
The response to immune checkpoint blockade, depends on a pre-existing, CD8 T cell-rich tumor microenvironment. (aacrjournals.org)
Thus, addressing the presence of immunosuppressive myeloid cell populations in the periphery and tumor microenvironment of patients with cancer is likely to be required for effective NK cell-based immunotherapy. (elifesciences.org)
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a very dense and highly organized tumor microenvironment (TME) consisting of extracellular matrix (ECM) proteins, cancer-associated fibroblasts (CAFs), pancreatic stellate cells (PSCs), and immune cells. (mdpi.com)
We review the relationship between TMB and the tumor immune microenvironment. (aacrjournals.org)
To address the limitations of the TMB, novel biomarkers are needed that account for the immunogenic quality of tumor mutations and capture the complexity of the tumor immune microenvironment. (aacrjournals.org)
The immune tumor microenvironment (TME) is a unique aspect of the response to immuno-oncology agents and measurement of single biomarkers does not adequately capture these complex interactions. (aacrjournals.org)
However, increasing data has indicated that the clinical potential of most immunotherapies is usually hampered by immunosuppressive status of the tumor microenvironment (TME) [ 7 ]. (thno.org)
Although it has been shown that the microenvironment of the liver is tolerogenic and impairs immune responses [ 3 ], antigen-specific T cell responses do occur [ 4 ]. (biomedcentral.com)
Two mechanisms have potential to impact the efficacy of immunotherapy when begun immediately after thermal ablation: mechanical changes in the tumor microenvironment and inflammatory-mediated changes in immune phenotype. (jci.org)
Early loss or exhaustion of CAR T cells, selection of CD19-negative clones, downregulation of CD19 expression, lineage switch of leukemia, and tumor microenvironment are important factors contributing to relapse after CAR T-cell therapy [ 9 , 10 ]. (biomedcentral.com)
HLA-G expression was later demonstrated in human tumors and was thought to play a role of Immunosuppression in the tumor microenvironment [2]. (symbiosisonlinepublishing.com)
Since that report more research has convinced us that HLA-G plays a major role of Immunosuppression in the tumor microenvironment. (symbiosisonlinepublishing.com)
This is due to the fact that even once tumor-antigen specific T cells are generated via vaccination, these T cells might not be effective in clearing the tumor because of the multiple inhibitor-mechanisms that are present in the tumor microenvironment. (cancernetwork.com)
Our group is studying interactions within the microenvironment of solid tumors that cause immune-suppression and tumor immune evasion. (cemm.at)
What factors drive T cell exhaustion in the tumor microenvironment and the draining lymph node? (cemm.at)
The microenvironment of solid tumors is characterized by a multitude of immune-suppressive factors, such as cytokines, high apoptotic cell load, unique extracellular matrix composition, hypoxia, scarcity of nutrients, metabolic waste products, and others. (cemm.at)
In addition to cancer cells, various immune cell subsets take part in shaping the suppressive tumor microenvironment, which in turn locally drives cancer-associated immune-regulatory phenotypes of monocytes, macrophages, fibroblasts and dendritic cells, often coupled with regulatory T cells and exhausted T cells that are unable to mount tumor-directed cytotoxic responses. (cemm.at)
Tumor-directed T cell responses are a prerequisite for successful immunotherapy, however, often T cells have an exhausted phenotype in the tumor microenvironment and fail to eliminate tumor cells. (cemm.at)
Gemcitabine is a standard agent used in the treatment of pancreatic cancer, with known effects on the tumor immune microenvironment. (amegroups.org)
Tumor-infiltrating CD8+ T-cells and myeloid cells, harvested after the mice were treated for 2 weeks, were analyzed with flow cytometry to characterize the effect the chemo-immunotherapy regimen had on the tumor microenvironment (TME). (amegroups.org)
Other factors have been suggested to correlate with response to immunotherapy based on clinical and preclinical studies, including elevated type 1 helper T cell (Th1) tumoral gene signature, [ 11 ] and IFN-γ expression, possibly attributable to its ties to other proteins and cytokines within the tumor microenvironment. (medscape.com)

Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. (elifesciences.org)
T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
Natural killer (NK) cell-based immunotherapy may overcome genetic mechanisms of resistance to T cell-based immunotherapy through antigen- and MHC-independent recognition of malignant cells. (elifesciences.org)
Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy. (nki.nl)
In a paper appearing in the June 29 edition of Cell , researchers led by Ben Youngblood, Ph.D. , an assistant member of the St. Jude Department of Immunology , reported findings that explain the failure of a form of immunotherapy called immune checkpoint blockade. (stjude.org)
The urgent need for novel treatments inspired me to pursue a research project in adoptive immunotherapy, genetically modifying Tcells to express artificial T cell receptors, termed chimeric antigen receptors (CARs), that target AML specific antigens. (stanford.edu)
Wargo and colleagues are working with the Parker Institute for Cancer Immunotherapy to develop a clinical trial that combines checkpoint blockade with microbiome modulation. (mdanderson.org)
Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better? (aacrjournals.org)
The development of immunotherapy is an important breakthrough for the treatment of cancer, with antitumor efficacy observed in a wide variety of tumors. (aacrjournals.org)
Recent advances in cancer immunology, highlighted by immune checkpoint inhibitors, have demonstrated that immunotherapy is a viable option in the oncologist's armamentarium. (ndltd.org)
This mechanistically rational antigen selection sequence, effective even for unvaccinated donors, regardless of HLA-haplotype, enables rapid identification of tumor protein regions relevant for cancer immunology, including adoptive immunotherapy, vaccines, and even identification of tumor neo-antigens unique to each patient. (ndltd.org)
Fig. 4: A lower level of CAR-mediated TROG-antigen expression was associated with improved clinical response to CAR-NK cell-based immunotherapy. (nature.com)
Wei X, Wang J, Liang M, Song M. Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy. (thno.org)
Immunotherapy is currently considered as a promising next-generation therapeutic strategy for various cancers thanks to its ability to modulate cell-specific immune responses toward tumors [ 1 ], which has gradually remodeled the landscape of clinical anticancer modality [ 2 ]. (thno.org)
Among most immunosuppressive cells, TAMs, as crucial drivers of immunosuppressive TME, account for the largest proportion of immune cells in the TME (approximately 50% of tumor mass) [ 9 , 10 ], which possess highly heterogeneity and play a complex regulatory role in tumor immunity and immunotherapy due to helping tumor evade immune surveillance [ 11 ]. (thno.org)
Moreover, TAMs usually display M2-like phenotypes that exert tumor-promoting role in TME, and promote production of related immunosuppressive factors that trigger immunotherapy resistance, including cytokines, chemokines, growth factors and soluble signaling mediators [ 12 ]. (thno.org)
He has focused the efforts of his research career on expanding the role of immunotherapy for gastrointestinal tumors and has aligned his clinical practice to coincide with his research interests. (ucsf.edu)
Further insights on the roles of CD8 + specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy. (bmj.com)
However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. (biomedcentral.com)
This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. (biomedcentral.com)
This has resulted in the development of additional immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and inhibitors of other immune checkpoints. (biomedcentral.com)
In a syngeneic model of epithelial cancer, we found that 7 days of immunotherapy (TLR9 agonist and checkpoint blockade), prior to thermal ablation, reduced macrophages and myeloid-derived suppressor cells and enhanced IFN-γ-producing CD8 + T cells, the M1 macrophage fraction, and PD-L1 expression on CD45 + cells. (jci.org)
When the tumor burden was increased by implantation of 3 orthotopic tumors, successive primed ablation of 2 discrete lesions resulted in survival of 60% of treated mice as compared with 25% of mice treated with immunotherapy alone. (jci.org)
In summary, we found that immunotherapy begun before ablation can be curative and can enhance efficacy in the presence of a high tumor burden. (jci.org)
Renewed interest in cancer immunotherapy has emerged by the introduction of targeted monoclonal antibodies and checkpoint blockade inhibitors. (symbiosisonlinepublishing.com)
We want to develop novel immunotherapy concepts by modulating and reprogramming specific immune cell compartments to achieve optimal immunity against tumors. (cemm.at)
Immunotherapy can take advantage of the immunogenic response that chemotherapy elicits in tumors. (amegroups.org)
The chemo-immunotherapy regimens also increased the number of tumor-infiltrating PD1+CD137+CD8+ T-cells and interferon-gamma-expressing PD1+CD137+CD8+ T-cells, but these increases were not statistically significant. (amegroups.org)
One way to elicit an immunogenic response to immune checkpoint inhibition may be chemotherapy, as many preclinical and clinical studies have demonstrated improved anti-tumor responses and survival with combination chemotherapy/immunotherapy regimens ( 1 - 4 ). (amegroups.org)
however, it is far from ideal because PD-L1-negative tumors may respond to immunotherapy and positive tumors may not. (medscape.com)

To evaluate the clinical activity, tolerability and anti-tumor activity of AM0010 alone or in combination with chemotherapy or immune checkpoint inhibitors a multi-basket phase 1 study was conducted. (aacrjournals.org)
Immune checkpoint inhibitors, including antibodies that block programmed cell death protein-1 (PD-1) and PD-L1, have transformed the management of many cancers. (aacrjournals.org)
Checkpoint inhibitors are emerging as among the most effective anticancer agents in our armamentarium. (aacrjournals.org)
The clinical success of immune checkpoint inhibitors has dramatically changed outcomes for patients across cancer types. (biomedcentral.com)
One probable mode of action for ICP inhibitors is the induction and/or restoration of T cell effector functions against individual somatic tumor mutations presented by HLA molecules (i.e., mutated neoepitopes) [ 9 ]. (biomedcentral.com)
We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein-protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). (nextbigfuture.com)
Initially, clinical trials evaluated immune checkpoint inhibitors (ICIs) in the salvage setting after platinum-based chemotherapy with mixed results in terms of efficacy. (unimi.it)
Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors. (cdc.gov)
This includes whether and how the immune system reacts to emerging tumours, whether antitumour immune responses are reactivated during treatment with immune-checkpoint inhibitors (ICIs), and whether unintended destructive immune pathologies accompany such treatment. (cdc.gov)
Recently, along with increasing use of immune checkpoint inhibitors such as nivolumab, the incidence of immune-related adverse events, including type 1 diabetes mellitus, has become a serious problem. (cdc.gov)
Immune checkpoint inhibitors (ICIs), including nivolumab, target programmed cell death protein-1 and have been used to treat malignancies, including melanoma, nonsmall cell lung cancer, and renal cell carcinoma. (cdc.gov)
Clinical course after immune checkpoint inhibitors treatment initiation for type 1 diabetes mellitus associated with nivolumab after second SARS-CoV-2 vaccination, Japan. (cdc.gov)

High tumor mutational burden (TMB-H) has shown promise as a biomarker in lung cancer, but the broad applicability of TMB-H as a biomarker of response across all solid tumors is unclear. (aacrjournals.org)
The FDA has approved the PD-1 inhibitor, pembrolizumab, as a therapy for all solid tumors with TMB equal to or greater than 10 mutations/megabase as measured by the FoundationOne CDx assay. (aacrjournals.org)
This approval was based on an exploratory analysis of the KEYNOTE-158 study, which was a single-arm, phase II multi-cohort study of pembrolizumab for select, previously treated advanced solid tumors. (aacrjournals.org)
Here, we elucidate the caveats of using TMB as a biomarker with a universal threshold across all solid tumors. (aacrjournals.org)
We highlight the risks of extrapolating evidence from a limited number of tumor histologies to all solid tumors, and we propose avenues for future research. (aacrjournals.org)
The FDA has approved the programmed cell death protein-1 (PD-1) inhibitor, pembrolizumab, in solid tumors with a tumor mutational burden (TMB) ≥ 10 mutations/megabase based on the FoundationOne CDx assay. (aacrjournals.org)
However, concerns exist whether TMB thresholds for predicting response to PD-1 blockade are equivalent across the spectrum of solid tumors, and there are scenarios where high TMB does not predict response. (aacrjournals.org)
On June 16, 2020, the FDA approved the programmed cell death protein-1 (PD-1) inhibitor, pembrolizumab (KEYTRUDA, Merck & Co., Inc.), for the treatment of tumor mutational burden-high (TMB-H) solid tumors. (aacrjournals.org)
In a phase II study of pembrolizumab in patients with microsatellite-high (MSI-H) solid tumors, the objective response rate was 39.6% (95% CI = 31.7% to 47.9%), including 7.4% complete responses (CRs) and 32.2% partial responses (PRs). (medscape.com)
Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. (msdmanuals.com)

Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. (elifesciences.org)
Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. (hindawi.com)
This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. (stanford.edu)
IL-2 and IFN-γ), immune checkpoint blockade (ICB) therapy (e.g., anti-PD-1/PD-L1 antibodies), and adoptive T-cell transfer (e.g., chimeric antigen receptor (CAR) T-cell therapy) [ 3 - 5 ]. (thno.org)
Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? (biomedcentral.com)
Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). (biomedcentral.com)
Chimeric antigen receptors (CAR) recognize specific proteins on the surface of tumor cells. (msdmanuals.com)

Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. (nih.gov)
The most active T cell endogenous inhibitory pathway is the immunoglobulin superfamily such as CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4): B7-1/B7-2 receptor/ligand grouping, which plays a central role in coordinating immune responses [ 7 , 8 ]. (hindawi.com)
The cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory activation-induced surface receptor on T cells that functions as a major negative regulator of anti-self-immune responses. (snmjournals.org)
Cell surface CTLA4 has 100-1,000 times higher affinity for the costimulatory molecules expressed by antigen-presenting cells, thereby efficiently competing with the positive costimulatory receptor CD28 ( 1 ). (snmjournals.org)
In the metastatic setting, it has been reported that 80% or more of these tumors express folate receptor alpha. (cancernetwork.com)

Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRβ sequencing. (bepress.com)
This review will discuss the metabolic changes that drive T cells into different stages of their development and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes. (elifesciences.org)
Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor targeting, and regression. (snmjournals.org)
Despite occasional cases of expansion of melanoma-specific T cells ( 14 , 15 ), the bulk of the data suggest that there is no detectable expansion of tumor antigen-specific lymphocytes, in particular when focusing on CD8+ T-cell responses. (snmjournals.org)
Current candidates in this area include PD-L1 expression, CD8 + tumor-infiltrating lymphocytes, tumor mutation load and neoantigen burden, immune-related gene signatures, and multiplex IHC assays that examine the pharmacodynamic and spatial interactions of the TME. (aacrjournals.org)
Most of them generally follow the same pathway to make immune-activated cytotoxic T lymphocytes (CTLs) abundantly infiltrate into tumor tissues and destroy tumor cells [ 6 ]. (thno.org)
Tumor-infiltrating lymphocytes (TILs) may have greater tumoricidal activity than LAK cells. (msdmanuals.com)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. (nih.gov)
Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses. (nih.gov)
OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. (bepress.com)
In contrast, ACT expands a patient's own T cells ex vivo to direct anti-tumor immunity when transfused back into the patient. (elifesciences.org)
Immune checkpoint (IC) proteins are some of the most important factors that tumor cells hijack to escape immune surveillance, and inhibiting ICs to enhance or relieve antitumor immunity has been proven efficient in tumor treatment. (portlandpress.com)
Our studies in patients and subsequent mouse research really drive home that our gut microbiomes modulate both systemic and anti-tumor immunity. (mdanderson.org)
Of note, the TME is rich in immunosuppressive cells (e.g., tumor-associated macrophages (TAMs), regulatory T cells (Tregs), immature dendritic cells (iDCs) and myeloid-derived suppressor cells (MDSCs)), that can suppress antitumor immunity as a result of secretion of various cytokines and chemokines, which enables tumor escape from immune surveillance [ 8 ]. (thno.org)
Identifying factors that control immunity and tolerance in order to direct antigen-specific immune responses for treating cancer and autoimmune disease. (mssm.edu)
Our ultimate goal is to identify cellular, molecular and spatial determinants that stimulate or suppress human tumor immunity and to target suppressive phenotypes, while enabling effector populations. (cemm.at)
We are exploring how polarization/restimulation with different tumor-associated antigen-presenting cells shape T cell phenotypes and how different antigen-presenting cell subsets and phenotypes drive or limit antigen-specific anti-tumor immunity. (cemm.at)

He completed his general surgery residency at Harvard University's Brigham and Women's Hospital and a tumor immunology post-doctorate fellowship in the laboratory of Dr. Steven Rosenberg in the Surgery Branch of the NIH/NCI, during which time he was first author on many of the initial phase I/II trials utilizing anti-CTLA4 antibodies. (ucsf.edu)
So, before you thought about exploring basic immunology in the context of cancer, you were initially focused on just the basic immunology side of the equation, looking at how T cells see regular or infected cells and their antigens? (cancerresearch.org)
There, she gained extensive knowledge of human tumor immunology and myeloid components of tumor immune suppression. (cemm.at)

Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. (thno.org)
Autologous as well as allogeneic CD8 + T cells transduced with tumor antigen specific T cell receptors (TCR) may cause significant tumor lysis upon adoptive transfer. (oncotarget.com)
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)
These MHC-bound antigens are what T cells-via their T cell receptors (TCRs)-interact with to determine if a cell is healthy or not. (cancerresearch.org)

Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity. (bepress.com)
In this investigation a human RCC tissue microarray (TMA) (n=374) predominantly consisting of the most common histological tumor subtypes was hybridized with an ERV-K env antibody and correlated with patient clinical data. (frontiersin.org)
The emerging clinical data suggest that a subset of patients with metastatic melanoma treated with CTLA4-blocking antibodies, in the range of 5%−15%, achieve durable objective tumor responses. (snmjournals.org)
Although ICB agents have shown outstanding clinical success, and their application has continued to expand to additional tumor types in the past decade, immune-related adverse events (irAEs) have been observed in a wide range of patients who receive ICB treatment. (portlandpress.com)
The clinical significance of T cell exhaustion is huge, because when a person comes into the clinic with a tumor, it is likely they have had it for many months," he said. (stjude.org)
Following completion of the Phase 1 part of the clinical trial, the Company opened enrollment for Phase 2 cohorts of 30 patients each in patients with melanoma, non-melanoma skin cancers, bladder cancer, and MSI-H tumors. (biospace.com)
Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). (thno.org)
In clinical practice, a key challenge for generating TIL products is the accessibility, quantity, and quality of tumor tissue in the era of neo-adjuvant therapy. (biomedcentral.com)

These agents, which inhibit the immune checkpoint proteins programmed death cell protein-1 (PD-1) or CTL associated antigen 4 (CTLA-4) are able to produce durable long-term remissions and are active in a broad range of tumor types, although not all patients respond ( 1-7 ). (aacrjournals.org)
Tripartite Motif Containing 13 (TRIM13), a member of TRIM proteins, is deleted in multiple tumor types, especially in B-cell chronic lymphocytic leukemia and multiple myeloma. (cancerindex.org)
My initial interest in the field revolved around wanting to understand the mechanisms that determine which pieces of viral proteins, known as antigens, are displayed on the cell surface by major histocompatibility complex (MHC) molecules. (cancerresearch.org)
9] have done a great job discussing HLA-G proteins in cancer and how they provide tumor cells with an immune escape mechanism. (symbiosisonlinepublishing.com)
In contrast to TCR T cells, CAR T cells recognize only relatively large proteins on the surface of tumor cells. (msdmanuals.com)

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. (nih.gov)
Monoclonal antibodies blocking CTLA4 induce regression of immunogenic tumors in mice ( 8 ) and are being pursued as a treatment approach for patients with cancer. (snmjournals.org)
There has been a great deal of interest shown in defining the mechanisms by which anti-CTLA4 antibodies induce tumor regressions in humans. (snmjournals.org)
Immune checkpoint blockade (ICB) agents such as antibodies blocking programmed death (PD) 1, PD-1 ligand (PD-L) 1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4 have been approved by the U.S. Food and Drug Administration (FDA) to treat several types of cancers. (portlandpress.com)
Antibodies blocking the immune checkpoint cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-1-ligand 1 (PD-L1) antigens have been tested in several gastrointestinal malignancies. (medscape.com)

thus, strategies to induce anti-tumor immune responses are needed. (ndltd.org)
Although immune checkpoint blockade (ICB) reinvigorates anti-tumor immune responses by disrupting co-inhibitory T-cell signaling, relapse frequently occurs after ICB treatment and acquired resistance often emergence after initial response [ 4 ]. (thno.org)

Two of the primary immunotherapies are immune checkpoint blockade (ICB) and adoptive cell transfer (ACT). (elifesciences.org)
Under grants awarded by the Department of Defense and National Institutes of Health (NIH), he works on designing novel immunotherapies (treatments that harness the immune system to fight tumors), particularly for liver metastases from colon cancer. (ucsf.edu)
Subsequently, the drug makes tumors much more susceptible to both chemotherapy and immunotherapies. (nextbigfuture.com)
In our group we aim to target immune-suppressive phenotypes of myeloid cells, paired with already established immunotherapies such as immune checkpoint blockade, to allow for optimal immune responses within the TME. (cemm.at)
The development of immunotherapies, particularly those blocking the immune checkpoint PD-1/PD-L1, has revolutionized lung cancer treatment. (cemm.at)

Pearce and her colleagues also found evidence that suggested cancer cells could disable T cells ability to fight off tumors and some kinds of infection. (wikipedia.org)
It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. (nih.gov)
Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. (bepress.com)
Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. (bepress.com)
These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. (bepress.com)
We will then examine how tumor cells create a toxic milieu for T cells that enter the TME. (elifesciences.org)
Background: The success of and the durability of immune therapy of cancer is thought to depend on the activation and expansion of tumor reactive and infiltrating CD8+ T cells. (aacrjournals.org)
IL-10 stimulates the antigen mediated cytotoxicity, survival and proliferation of intra-tumoral CD8+ T cells and simultaneously dampens chronic inflammation. (aacrjournals.org)
IL-10 activates with STAT3 an essential survival and proliferation signal in antigen activated CD8 T cells. (aacrjournals.org)
PDF) Kraan J, van den Broek P, Verhoef C, Grunhagen DJ, Taal W, Gratama JW, Sleijfer SEndothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells. (researchgate.net)
Results: No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. (researchgate.net)
Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. (elifesciences.org)
However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. (hindawi.com)
Various biological processes including immunoreaction of infection, tumor prevention, and human aging could cause telomere damage, tumor-related stress responses, and T regulatory (Treg) cells activation, which even trigger T cell senescence showing the distinctive phenotypic and functional alternation [ 9 , 10 ]. (hindawi.com)
It provides a dominant negative signaling to T cells on binding to the costimulatory molecules CD80 (B7.1) and CD86 (B7.2) expressed on the surface of antigen-presenting cells ( 1 ). (snmjournals.org)
In vitro, PD-1 + γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. (nki.nl)
By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. (nki.nl)
In this treatment, patients receive a drug that releases the brakes on their T cells allowing them to kill virally infected or tumor cells. (stjude.org)
The tumor-fighting T cells detect a protein called an antigen on the cancer cells' surface that triggers the attack. (stjude.org)
And their T cells, which would be responding to that tumor, have been exposed to the tumor antigen for a long time. (stjude.org)
They found the culprit was a so-called "epigenetic program" that repressed the T cells' ability to respond to tumor antigens. (stjude.org)
They also found that the exhaustion program persisted, even after the T cells were not exposed to the triggering antigen. (stjude.org)
The researchers found that treating the T cells with a widely used immune-checkpoint inhibitor called PD-1 did not erase the epigenetic exhaustion finding. (stjude.org)
However, when researchers treated mice that had tumors with the chemotherapy drug decitabine, their T cells showed properties indicating enhancement. (stjude.org)
Immune checkpoint blockade drugs that free the body's own immune system to attack cancer cells help around 25 percent of metastatic melanoma patients, and those responses are not always durable. (mdanderson.org)
Hot spot" peptide Ag-specific T-cells preferentially recognized endogenous tumor derived MUC1, either in MUC1 expressing tumor cell killing assays (p=0.038, compared to non-peptide Ag-specific T-cells) or as MUC1 tumor lysate when pulsed onto restimulatory PBMC (p=0.022 and 0.025, for CD4+ and CD8+ T-cells, respectively, compared to T-cells directed against peptides from non-hot spot regions). (ndltd.org)
In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning. (thno.org)
Importantly, T cells artificially expressing the MAGE-A3-Mp4 specific TCRs exhibited strong MAGE-A3+ tumor cell recognition and killing effect. (thno.org)
This phenomenon could be offset by a dual-CAR system incorporating both an activating CAR against the cognate tumor antigen and an NK self-recognizing inhibitory CAR that transferred a 'don't kill me' signal to NK cells upon engagement with their TROG + siblings. (nature.com)
Fig. 1: CAR19-mediated trogocytosis in NK cells cocultured with CD19 + tumor targets. (nature.com)
Tetramer staining was performed to determine the frequency and avidity of CD8 + T cells targeting the tumor-specific epitope GSW11 and confirmed with tetramer competition assays. (bmj.com)
High avidity T cells (Tet hi ), if present, were only found in progressing PD-1 refractory tumors. (bmj.com)
One is the ability to administer large numbers of highly selected cells with high avidity for tumor antigens that can recognize shared and patient-specific mutated (neo) antigens. (biomedcentral.com)
Successful TIL therapy starts with the identification, enrichment, stimulation, and expansion of potent tumor-reactive T cells. (biomedcentral.com)
G - I ) The entire fourth and ninth mammary fat pad (tumor and embedded lymph node) was harvested at day 28, and immune cells were quantified by flow cytometry ( n = 4 per group). (jci.org)
Effect of therapy on ( G ) IFN-γ CD4 + T cells, ( H ) CD8 + T cells, and ( I ) Tregs in the treated and contralateral tumors. (jci.org)
Studying novel approaches to enhance adaptive immune responses against cancer, including manipulating checkpoint blockades, and in situ vaccine strategies to mobilize and activate dendritic cells (DC) to present tumor-associated antigens. (mssm.edu)
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)
This master thesis is a part of a project aiming to set up immunoaffinity-purification/MS based method in order to analyse the ligandome and determine T-cell recognized cancer associated antigens from tumor cells. (helsinki.fi)
Yeah, my work has led me to cancer neoantigens, but it started at the much more fundamental level of how antigens are presented by cells infected by viruses, and how these cells are then recognized by T cells. (cancerresearch.org)
which allows the escape of tumor cells from Natural Killer Cell (NK) and cytotoxic CD8+ T-cell destruction. (symbiosisonlinepublishing.com)
HLA-G induces tolerance and tumor Immunosuppression by inhibiting various immune-competent cells. (symbiosisonlinepublishing.com)
Others have reported that HLA-G antigens are expressed on tumor infiltrating cells and can be detected in the blood of cancer patients. (symbiosisonlinepublishing.com)
One such cytokine is IL-10, a powerful immunosuppressive cytokine, which confers immunoprotection to tumor cells and promotes metastases. (symbiosisonlinepublishing.com)
Questions that fuel our research are: How can we empower antigen-presenting cells to prime effective tumor-directed T cell responses? (cemm.at)
What specific pathways need to be targeted in tumor-associated myeloid cells to break their immune-suppressive properties? (cemm.at)
Exhausted T cells are functionally defined by limited cytokine production and cytotoxic effector function and inefficiency to clear the cellular source of antigen. (cemm.at)
Unlike functional memory and effector T cells, exhausted T cells are dependent on persistence of presented antigen. (cemm.at)
PD-L1 expression on both infiltrating immune cells and/or tumor cells can be predictive for therapeutic success of ICB, suggesting that multiple mechanisms for T cell suppression involving PD-L1 expression on different compartments exist. (cemm.at)
In her main work, she uncovered a regulatory module expressed in dendritic cells in human non-small-cell lung cancer patients, functionally validated multiple of these regulatory molecules, and showed that modulating the regulatory program in dendritic cells leads to improved tumor control. (cemm.at)
Jim Allison found a way to remove the brakes that stop T cells from fighting tumor cells - a discovery that opens brand new and very effective ways to treat cancer," said Joseph Goldstein, M.D., chair of the Lasker Medical Research Awards Jury, Nobel Laureate and chair of Molecular Genetics at The University of Texas Southwestern Medical Center in Dallas. (mdanderson.org)
A number of immunologic interventions, both passive and active, can be directed against tumor cells. (msdmanuals.com)
Lymphokine-activated killer (LAK) cells are produced from the patient's T cells which are extracted from the tumor and grown in a cell culture system with the lymphokine interleukin-2 (IL-2). (msdmanuals.com)
However, the progenitor cells consist of T cells isolated from resected tumor tissue. (msdmanuals.com)
This process theoretically provides a line of T cells with greater tumor specificity than those obtained from the blood. (msdmanuals.com)
Антигени пухлин Many tumor cells produce antigens, which may be released in the bloodstream or remain on the cell surface. (msdmanuals.com)
TAAs) with high specificity to tumor cells. (msdmanuals.com)
Concomitant use of interferon enhances the expression of major histocompatibility complex (MHC) antigens and TAAs on tumor cells, thereby augmenting the killing of tumor cells by the infused effector cells. (msdmanuals.com)

An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations. (biomedcentral.com)

Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. (nih.gov)
Although epigenetically silenced, endogenous retroviral (ERV) genes become activated in tumors and function to ignite immune responses. (frontiersin.org)
However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. (thno.org)
Methods CT26 models were treated with anti-PD-1 on days 3, 6 and 9 following subcutaneous tumor implantation generating variable responses during early tumor development. (bmj.com)
Adoptive transfer of Tet lo showed more effective tumor control than Tet hi , and curative responses were achieved when Tet lo was combined with two doses of anti-PD-1. (bmj.com)
PD-1 blockade induces responses by inhibiting adaptive immune resistance. (histopat.es)
Following small-molecule compound C26-A6 treatment to disrupt the MTDH-SND1 complex, we showed enhanced immune surveillance and sensitivity to anti-programmed cell death protein 1 therapy in preclinical models of metastatic breast cancer, in support of this combination therapy as a viable approach to increase immune-checkpoint blockade therapy responses in metastatic breast cancer. (nextbigfuture.com)

In preclinical model systems studying viral infections or tumors, the researchers found that a chemotherapy drug already in use can reverse that exhaustion. (stjude.org)
In preclinical studies, the researchers explored the mechanism by which both viral infection and a tumor caused T cell exhaustion. (stjude.org)

Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. (histopat.es)

Patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) often have clinicopathological characteristics associated with poor prognosis, such as high tumor burden and high-risk gene mutations. (biomedcentral.com)

At the conference, Dr. Zamarin presented data from a phase II trial at Memorial Sloan Kettering, of a peptide vaccine called TPIV-200 in combination with durvalumab, an anti-PD-1 checkpoint inhibitor antibody, in patients with platinum-resistant ovarian cancer. (cancernetwork.com)
We report a patient who had immune checkpoint inhibitor‒associated type 1 diabetes mellitus that developed after a second mRNA-based SARS-CoV-2 vaccination. (cdc.gov)
this form of diabetes has been called immune checkpoint inhibitor‒induced diabetes mellitus ( 5 ). (cdc.gov)
We report a patient who had checkpoint inhibitor‒induced diabetes mellitus develop after he received a second mRNA-based SARS-CoV-2 vaccination. (cdc.gov)
The first randomized phase III trial to investigate a checkpoint inhibitor in gastric cancer was the ONO-4358 study. (medscape.com)

There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
Recent data suggest that MPM is an immunologically active tumor, in which checkpoint inhibition through the blockade of the anti-cytotoxic T lymphocyte antigen-4 (-CTLA-4) or anti-programmed cell death 1 (PD-1) could play a major therapeutic role. (unimi.it)

Molecular imaging with the PET probe 18 F-FLT allows mapping and noninvasive imaging of cell proliferation in secondary lymphoid organs after CTLA4 blockade in patients with metastatic melanoma. (snmjournals.org)
The researchers found the enhanced T cell proliferation was coupled with significant control of tumor growth. (stjude.org)

We hypothesized that many tumor associated antigens (Ag) are readily susceptible to immune attack, but only in the context of identifying the tumor antigen epitopes that can reliably initiate an immune response, regardless of individual patient human leukocyte antigen (HLA) haplotype restrictions. (ndltd.org)
Human leukocyte antigen G (HLA-G) is an immunotolerant non-classical major histocompatibility complex 1b molecule. (symbiosisonlinepublishing.com)
Human leukocyte antigen typing identified no specific alleles, including DR4, known to be related to T1D ( Table ). (cdc.gov)

There is a significant unmet need for predictive biomarkers that can reliably identify patients who derive a clinically meaningful response from PD-1/PD-L1 blockade. (aacrjournals.org)

Fig. 2: Impact of antigen-induced self-engagement on CAR-NK effector cell phenotype and function. (nature.com)

The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. (bepress.com)

The findings suggest that combining epigenetic reprogramming with immune-checkpoint blockade could enhance treatment efficacy. (stjude.org)

Patients with metastatic melanoma treated with anti-PD1 checkpoint blockade have their disease controlled longer if they have a more diverse population of bacteria in the gut or an abundance of certain types of bacteria, according to the team's analysis of fecal samples to assess patients' gut microbiomes. (mdanderson.org)
My research interests comprise cutaneous tumors with emphasis in lymphomas and melanoma. (mdanderson.org)
Drugs using this approach, called immune checkpoint blockade, now are approved for treating late-stage melanoma and lung cancer. (mdanderson.org)

High ERV-K env total protein expression of all tumor subtypes significantly correlated with low tumor grading and a longer disease specific survival using multivariable analyses. (frontiersin.org)
Methods: Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay. (researchgate.net)
3] was first to show evidence that HLA-G protein expression could play a role in tumor escape from the host immune system in 1998. (symbiosisonlinepublishing.com)

Here, the underlying mechanisms of tumor immunosuppression caused by TAMs are first emphatically elucidated, and then the basic design of TAMs-focused immune-nanomedicines are discussed, mainly including diverse categories of nanomaterials, targeted and stimulus-responsive modifications, and TAM imaging in nanomedicines. (thno.org)
4] has investigated the complexities of HLA-G as an immunomodulatory molecule, and its role in tumor immunosuppression. (symbiosisonlinepublishing.com)

Research has intensified to understand ERV protein function and their role as tumor antigens and targets for cancer (immune) therapy. (frontiersin.org)
Since these mutated HLA ligands were unacquainted to the immune system before carcinogenesis, they have been proposed as ideal tumor-specific targets [ 10 , 11 ]. (biomedcentral.com)

Transcriptomics analyses showed pathways related to TCR signaling, cytotoxicity and oxidative phosphorylation were significantly enriched in Tet lo found in both regressing and progressing tumors compared with Tet hi , whereas genes related to DNA damage, apoptosis and autophagy were downregulated. (bmj.com)

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)

Kang and his colleagues have shown that MTDH has two primary mechanisms: it helps tumors survive stresses they commonly experience as they grow or under the treatment of chemotherapy, plus it muzzles the alarm cry coming from organs invaded by tumors. (nextbigfuture.com)
That's the best of all worlds: two mechanisms attacking a tumor, very few side effects on normal tissues, and best of all, this is not for one specific kind of cancer, but for all major kinds of cancers. (nextbigfuture.com)
Paradoxically, the mechanisms of action of PD-1/PD-L1 blockade are still incompletely understood and only a subset of patients responds to immune checkpoint blockade (ICB). (cemm.at)

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. (bepress.com)
At the epicenter of this dynamic and complex TME lies the cancer stem cell (CSC), which is believed to be the root of the tumor and the cell responsible for chemoresistance and disease relapse. (mdpi.com)
Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. (nextbigfuture.com)
One of the limitations of cancer vaccines against shared antigens in different cancers in general is that the overexpression of some of these antigens is restricted to only a subset of tumors. (cancernetwork.com)
EBV-positive tumors have a higher frequency of Crohn's disease-like lymphoid reaction that correlates with an improved prognosis in patients with gastric cancer. (medscape.com)

HLA-G has the ability to modulate and cause release of cytokines directing the tumor micro-environment to a Th2 profile. (symbiosisonlinepublishing.com)

NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing Liver disease Positive hepatitis B surface antigen test at screening Patients known to be positive for hepatitis C virus antibody HIV infection, patients are excluded if HIV is not adequately controlled (specific criteria apply). (who.int)

0.05), and trended towards decreasing tumor-associated macrophages (TAMs) (P=0.18). (amegroups.org)

Treatment of xenograft tumors resulted in PD-L1-dependent tumor growth inhibition. (elifesciences.org)
Thermal ablation is an appealing modality to pair with such protocols, as tumors can be rapidly debulked (cell death occurring within minutes to hours), tumor antigens can be released locally, and treatment can be conducted and repeated without the concerns of radiation-based therapies. (jci.org)
D - F ) NDL tumor growth following MRgFUS ablation ( n = 7) compared with no-treatment (NT) control NDL tumor growth ( n = 34 total, 8 representative growth curves shown for this individual study). (jci.org)
Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. (bvsalud.org)
[ 10 ] Based partly on this study, pembrolizumab was recently approved by the FDA for treatment of advanced MSI-H tumors. (medscape.com)

What antigen-presenting cell phenotypes play a role in T cell polarization and restimulation at the tumor site and how do they drive/limit T cell exhaustion? (cemm.at)
Hence, direct antigen-presenting cell/T cell contact is critical in driving T cell exhaustion. (cemm.at)

K - M ) H&E staining performed at day 31 confirmed that, compared with ( K ) control tumors ( n = 3), viable tumor was reduced in ( L ) treated tumors ( n = 3), where residual viable tumor tissue (red arrows) existed outside the path of the ultrasound beam. (jci.org)
Thermal ablation did not reduce viable ( M ) contralateral tumor tissue ( n = 3). (jci.org)
Uroservic and Dammer [5] suggested that HLA-G was associated with tumor progression and growth, and that it was mainly detected in tumor tissue and rarely in adjacent normal tissue. (symbiosisonlinepublishing.com)

As a result, the functionality of many different immune and stromal cell populations is compromised, and tumor immune evasion is facilitated. (cemm.at)

Anatomy20

Organisms12

Diseases30

Chemicals and Drugs105

Analytical, Diagnostic and Therapeutic Techniques and Equipment29

Phenomena and Processes67

Disciplines and Occupations1

Information Science3

Health Care5

Microenvironment23

Immunotherapy30

Inhibitors12

Solid tumors10

Chimeric8

Receptor5

Lymphocytes7

Immunity10

Immunology3

Receptors4

Clinical8

Proteins5

Antibodies5

Anti-tumor immune responses2

Immunotherapies5

Cells58

Mutational burden1

Responses7

Preclinical2

Immunogenic1

Mutations1

Inhibitor5

Cytotoxic2

Proliferation2

Human leukocy3

Biomarkers1

Effector1

Lymphocyte1

Efficacy1

Melanoma3

Expression3

Immunosuppression2

Targets2

Genes1

Cytokine1

Mechanisms3

Cancer5

Cytokines1

Patients1

Macrophages1

Treatment5

Exhaustion2

Tissue3

Populations1