• While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. (mdpi.com)
  • Another approach relies upon the use of chimeric antigen receptors (CARs) that directly target cancer cells or immunosuppressive cellular elements in the tumor microenvironment. (upenn.edu)
  • The tumor microenvironment of malignant gliomas is usually immunosuppressive,22 and this has been shown after CAR T?cell infusion.10 Immune checkpoint receptors (e.g. (campaignfornonviolentschools.org)
  • In the tumor microenvironment, tumor-associated macrophages (TAMs) display an array of phenotypes beyond the M1/M2 paradigm, ranging from antitumoral to immunosuppressive, proangiogenic, immunomodulatory and tissue-remodeling phenotypes ( 7 - 9 ). (frontiersin.org)
  • Another myeloid population in the tumor microenvironment (TME) are DCs, that originate from different precursors and display various phenotypes, ranging from immunosuppressive monocyte-derived DCs (Mo-DCs) to immunocompetent cDC1 and cDC2 subsets ( 22 ). (frontiersin.org)
  • Tumor purity-related coexpression factors in the tumor microenvironment have essential clinical, genomic, and biological significance in lung cancer. (hindawi.com)
  • Tumor microenvironment possesses complexity because of a mixture of growth-promoting and inhibiting growth factors, nutrients, chemokines, and other noncancer types, which interact with each other and associate with tumor growth, disease progression, drug resistance, and especially, infiltrating T lymphocytes and tumor growth [ 2 ]. (hindawi.com)
  • We explored the coexpression factors most related to tumor purity and related biological functions and demonstrated the most relevant biological functions and mechanism of action affecting tumor purity in the lung cancer tumor microenvironment. (hindawi.com)
  • Increased tryptophan (Trp) catabolism in the tumor microenvironment (TME) can mediate immune suppression by upregulation of interferon (IFN)-gamma-inducible indoleamine 2,3-dioxygenase (IDO1) and/or ectopic expression of the predominantly liver-restricted enzyme tryptophan 2,3-dioxygenase (TDO). (bioxcell.com)
  • CD4 + T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. (nature.com)
  • Mechanistic investigation defined that Axl inhibition reprograms the immunological microenvironment leading to the increased proliferation, activation and effector function of tumor-infiltrating CD4 + and CD8 + T cells possibly through preferential accumulation and activation of CD103 + cross-presenting dendritic cells. (oncotarget.com)
  • γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. (explorationpub.com)
  • Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. (explorationpub.com)
  • While many successful immunotherapeutic regimens have relied on checkpoint inhibition, other immunotherapeutic approaches, such as adoptive cellular therapies (ACT), the use of bispecific antibodies, and targeting components of the tumor microenvironment, are showing promise in a variety of cancer types. (aacr.org)
  • An immune cell in the tumor microenvironment that may be important for inhibiting the immune response against bladder cancer is the myeloid derived suppressor cell (MDSC). (iospress.com)
  • Integrative analyses of similar to 500 mice and similar to 1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. (unav.edu)
  • Objectives Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. (bmj.com)
  • 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)
  • Increasing evidence indicated that conventional and targeted therapies could affect tumor-associated immune responses and increase the effectiveness of immunotherapy. (biomedcentral.com)
  • Therefore recent initiatives in immunotherapy of cancers have centered on activating the dampened disease fighting capability by inhibiting the immune system checkpoint pathways in charge of T cell paralysis. (opioid-receptors.com)
  • Vaccination and T cell-based immunotherapy rely on one important feature of the adaptive immune system: the ability to form long-lasting memory cells able to rapidly respond to a second exposure with the same antigen [ 1 - 3 ]. (bmj.com)
  • Over the past decade, cancer immunotherapy has been steering immune responses toward cancer cell eradication. (frontiersin.org)
  • In cancer immunotherapy, the field has concentrated on two related modalities: First, targeting cancer antigens through highly activated chimeric antigen T cells (CAR-Ts) and second, re-animating endogenous quiescent T cells through checkpoint blockade. (umn.edu)
  • 2016). "Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses" Nat Med. (bioxcell.com)
  • Because tumour dormancy provides a unique therapeutic window to prevent metastatic disease, we discuss on-going clinical trials and weigh the potential for immunotherapy to eradicate dormant disease. (nature.com)
  • 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)
  • State-of-the art tumour-genome sequencing and analysis is enabling researchers to provide uniquely personalized immunotherapy. (nature.com)
  • The aim of immunotherapy is to treat cancer by enabling the immune system to attack the tumour. (nature.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)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer. (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)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022). (biomedcentral.com)
  • Thus, Axl-directed therapy in Axl expressing tumors could hold a great potential to subvert the innate and/or adaptive resistance to and broaden the coverage of population benefited from ICB-based immunotherapy. (oncotarget.com)
  • To determine if the improved response to treatment in the absence of iNKT cells was independent from the immunotherapy employed, 4T1-tumor bearing WT and iNKT −/− mice were treated with local radiotherapy in combination with antibody-mediated CD137 co-stimulation. (biomedcentral.com)
  • The third plenary session of the AACR Annual Meeting 2019 , titled "Manipulating the Immune System in Cancer Therapy," focused on recent advances in the field of immunotherapy. (aacr.org)
  • Several types of ACT round out the immunotherapy arsenal, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) therapy, and tumor-infiltrating lymphocyte (TIL) therapy. (aacr.org)
  • The current research aims to better understand the vaccination mechanisms and develop ways to influence the suppressive environment in tumors to allow effective immunotherapy. (universiteitleiden.nl)
  • Studies to antigen uptake, processing and presentation to T cells, the biology of dendritic cells and the regulation of immunity are aimed to raise our understanding of the immune reactions to tumor cells and improve immunotherapy of cancer. (universiteitleiden.nl)
  • Dijke, P. ten & Cruz, L.J. (2023), Enhancing anti-tumor immunity through liposomal oxaliplatin and localized immunotherapy via STING activation, Journal of Controlled Release 357: 531-544. (universiteitleiden.nl)
  • Background Neoantigens, new immunogenic sequences arising from tumor mutations, have been associated with response to immunotherapy and are considered potential targets for vaccination. (unav.edu)
  • Cancer immunotherapy consists of multiple approaches that harness and enhance the innate powers of the immune system to fight the disease. (technologynetworks.com)
  • Various immunotherapy tumor-targeting schemes. (technologynetworks.com)
  • Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. (oncotarget.com)
  • These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. (oncotarget.com)
  • PD-1 axis blockade has been proven time and again to be a successful immunotherapy for a wide variety of cancer types, and it is assumed to work by reversing or preventing T cell exhaustion. (acir.org)
  • However, the exact way by which this cancer immunotherapy works has not been fully elucidated, and recent studies have shown that the mechanism behind PD-1 axis blockade may be more complex than previously thought. (acir.org)
  • Passive cellular immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (msdmanuals.com)
  • The presence of TAMs in most solid tumors is correlated with poor prognosis and overall survival of patients ( 10 ). (frontiersin.org)
  • In addition to TAMs, solid tumors are also infiltrated by immunosuppressive, immature myeloid progenitor cells, commonly referred to as monocytic or polymorphonuclear myeloid-derived suppressor cells (M/PMN-MDSC) ( 11 - 13 ). (frontiersin.org)
  • In this report, the biologic functions of MDSC are defined and evidence linking MDSC with the response to cancer immunotherapies in solid tumors are reviewed. (iospress.com)
  • Background Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. (gpdunnlab.com)
  • Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. (msdmanuals.com)
  • This understanding has led to a concerted work to build up targeted immunotherapeutic methods to cancer with the blockade of immune system checkpoint receptors. (opioid-receptors.com)
  • Unexpectedly, in the murine tumor model, we found that virtually all TIL-Treg-expressing T cell receptors that are specific for TAA fully develop a distinct TH1-like signature over a 2-week period after entry into the tumor, down-regulating FoxP3 and up-regulating expression of TBX21 (Tbet), IFNG, and certain proinflammatory granzymes. (bvsalud.org)
  • One approach relies on the isolation and cloning of T cell receptors (TCRs) that confer non-reactive T cells with specific and potent immune function following gene transfer. (upenn.edu)
  • Introducing chimeric antigen receptors into the endogenous T-cell receptor locus reduces tonic signalling, averts accelerated T-cell differentiation and delays T-cell exhaustion, leading to enhanced function and anti-tumour efficacy compared to random integrations. (nature.com)
  • 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)
  • LECs can modulate dendritic cell function, present antigens to T cells on MHC class I and MHC class II molecules, and express immunomodulatory cytokines and receptors, which suggests that their roles in adaptive immunity are far more extensive than previously realized. (jci.org)
  • Chimeric antigen receptors (CAR) recognize specific proteins on the surface of tumor cells. (msdmanuals.com)
  • At that time, it was concluded that B7-H1 helps tumor cells evade anti-tumor immunity. (wikipedia.org)
  • Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. (elifesciences.org)
  • In each of these strategies, the therapeutic goal is to re-ignite T-cell immunity, in order to eradicate tumors. (umn.edu)
  • Relationship between hematogenous tumor cell dissemination and cellular immunity in DCIS patients. (nature.com)
  • However, this finding has triggered further interest in utilising tumour-specific MHC-II to harness sustained anti-tumour immunity through the activation of CD4 + T helper cells. (portlandpress.com)
  • Thus, their reactivation represents an attractive way to unleash anti-tumour immunity. (portlandpress.com)
  • Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. (biomedcentral.com)
  • Natural killer T (NKT) cells comprise a subset of lymphocytes originating from a distinct developmental lineage [ 1 ] which bridge innate and adaptive immunity and modulate immune responses in autoimmunity, malignancies and infections [ 2 ]. (biomedcentral.com)
  • Thus, monocyte depletion by gemcitabine administration reduced the generation of these DC and increased vaccine-induced immunity, which rejected about 20% of LLC-OVA and B16-OVA tumors, which are non-responders to anti-PD-1. (unav.edu)
  • set out to explore the role of different myeloid cell populations in the regulation of T cell immunity and PD-1/PD-L1 blockade. (acir.org)
  • Despite the profound and sustained anti-tumor responses observed in treating ovarian cancer patients, resistance to PARP inhibitors has emerged in some cases [ 8 ]. (biomedcentral.com)
  • It has been shown that responses to these agents are related to the mutagenic burden, such as in tumors with BRCA and other homologous recombination (HR) proteins deficiencies [ 10 ]. (biomedcentral.com)
  • In our study, we investigated the dynamic changes and responses of immune cells and cytokines during Niraparib treatment. (biomedcentral.com)
  • however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. (bvsalud.org)
  • Other current efforts include the exploration of immunomodulation to potentiate endogenous antitumor T cell responses, use of bispecific antibodies, pharmacological sensitization of tumor cells to immune attack, tumor vasculature targeting, preclinical validations, clinical translation and trial support. (upenn.edu)
  • Background The development of memory responses is an evolutionary function of the adaptive immune system. (bmj.com)
  • Immune cells abundantly infiltrate tumors, creating a complex environment mediated by repetitive cycles of antitumor responses and immune evasion ( 1 ). (frontiersin.org)
  • Myeloid innate immune cells, such as granulocytes, monocytes, macrophages and dendritic cells (DCs), play an important role in cancer-cell recognition, initiation of inflammation and antitumor responses ( 2 ). (frontiersin.org)
  • Hence, myeloid cells play a dual role in cancer as they can initiate antitumor responses and communicate with cells of the adaptive immune system, but also promote local inflammation leading to chronic cancer-associated inflammation ( 5 , 6 ). (frontiersin.org)
  • The innate immune response by myeloid cells occurs as a succession of events starting at signaling through cytosolic or surface PRRs, followed by effector responses including the release of cytokines, reactive oxygen species (ROS), reactive nitrogen species (RNS), antibacterial peptides and degranulation ( Figure 1 ). (frontiersin.org)
  • These include blockade of co-stimulation pathways and agonism of coinhibitory pathways, in order to achieve the delicate state of balance that is transplant tolerance: a state which guarantees lifelong transplant acceptance without ongoing immunosuppression, and with preservation of protective immune responses. (umn.edu)
  • thus, strategies to induce anti-tumor immune responses are needed. (ndltd.org)
  • However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. (thno.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)
  • By blocking the negative immune regulatory signals mediated by PD-1/PD-L1 pathway, these drugs remove the inhibition of T-cell activation and effector function and vigorously restore antitumor immune responses [ 3 ]. (oncotarget.com)
  • iNKT cells can promote the polarization of adaptive immune responses towards both Th1 and Th2 and can secrete immunosuppressive cytokines [ 19 ]. (biomedcentral.com)
  • Emerging research on the roles of stromal cells in modulating adaptive immune responses has included a new focus on lymphatic endothelial cells (LECs). (jci.org)
  • In this Review, we highlight these connections to reveal new roles of LECs, along with their transport functions, in modulating adaptive immune responses. (jci.org)
  • studies examining the mechanisms and efficacy of a novel cellular tumor vaccine strategy that uses antigen-loaded monocytes and an endogenous antigen transfer pathway to stimulate potent anti-tumor T cell responses (Project 3). (cancer.gov)
  • TAA has been tested previously against glioblastoma with minimal success, partly due to insufficient CD8+ T cell responses to low level antigen expression of individual epitopes. (cancer.gov)
  • Aim 2 is conducting preclinical work to determine if CDX-527 simultaneously depletes TRegs based on prior data of CD27-mediated Treg depletion and increases vaccine-induced immune responses. (cancer.gov)
  • Myeloid derived suppressor cells (MDSC) are immune cells that dampen immune responses. (iospress.com)
  • Pre-clinical evidence suggests that MDSC suppress anti-tumor immune responses. (iospress.com)
  • Immune checkpoint blockade can lead to durable complete responses for some patients, but overall objective response rates are only 15-31% [ 2-4 ]. (iospress.com)
  • The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. (gpdunnlab.com)
  • Immunomodulatory signals from the extracellular matrix help to shape immune responses. (bmj.com)
  • One important cause of impaired erythroid responses in children with SMA is dysregulation in the innate immune response. (ijbs.com)
  • Together, these experiments showed that PD-L1 expression on antigen-presenting cells (APCs) played a role in antitumor T cell responses via PD-1 interactions. (acir.org)
  • Analysis of T cell responses at day 10 post inoculation revealed increased frequency and number of CD8 + T cells within PD-L1-deficient MC38 tumors of PD-L1 KO and PD-L1 ΔDC mice compared to WT controls. (acir.org)
  • The results of the present study indicate that microRNAs play important roles in regulating asthma immune responses. (cdc.gov)
  • Immune checkpoint blockades (ICBs) therapy showed limited efficacy in ovarian cancer management. (biomedcentral.com)
  • Here, we found that Axl inhibition by tyrosine kinase inhibitors induces antitumor efficacy critically depending on immune effector mechanisms in two highly clinical relevant murine tumor models. (oncotarget.com)
  • More importantly, we show that Axl inhibition induces an adaptive immune resistance evidenced by unregulated PD-L1 expression on tumor cells and combined Axl inhibition with PD-1 blockade mounts a potent synergistic antitumor efficacy leading to tumor eradication. (oncotarget.com)
  • According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)
  • The therapeutic efficacy of neoantigen-specific T cells was assessed through a model of cellular therapy consisting of the transfer of activated MISTIC T cells and interleukin 2 into lymphodepleted tumor-bearing mice. (gpdunnlab.com)
  • The efficacy of MISTIC T cell therapy was lost in mice bearing a tumor with heterogeneous mImp3 expression, showcasing the barriers to targeted therapy in polyclonal human tumors. (gpdunnlab.com)
  • This improved efficacy was associated with higher tumor T-cell infiltration and overexpression of PD-1/PD-L1. (unav.edu)
  • B16-OVA tumors benefited from a synergistic effect, reaching 75% of tumor rejection, but higher levels of exhausted T-cells in LLC-OVA tumors co-expressing PD-1, LAG3 and TIM3 precluded similar levels of efficacy. (unav.edu)
  • While many methods have been developed to screen and evaluate the efficacy of immune cell‑mediated killing, there is a need for a more robust in vitro assay to accurately predict the in vivo behavior of therapies. (technologynetworks.com)
  • While the data provided by these assays help piece together an understanding of different facets of immune cell‑mediated killing, it is important to note that the parameters being reported often do not correlate with target cell killing efficacy in vivo. (technologynetworks.com)
  • Tumors exploit multiple immunosuppressive pathways to positively evade immune system identification including endogenous "immune system checkpoints" that normally terminate immune system replies after antigen activation. (opioid-receptors.com)
  • A key mechanism of immune evasion deployed by tumour cells is to reduce neoantigen presentation through down-regulation of the antigen presentation machinery. (portlandpress.com)
  • MHC-I and MHC-II proteins are key components of the antigen presentation machinery responsible for neoantigen presentation to CD8 + and CD4 + T lymphocytes, respectively. (portlandpress.com)
  • Conclusions We generated and characterized the first TCR transgenic against an endogenous neoantigen within a preclinical glioma model and demonstrated the therapeutic potential of adoptively transferred neoantigen-specific T cells. (gpdunnlab.com)
  • We determined that, in addition to infiltrating the brain tumor parenchyma itself, cDC1 prime neoantigen-specific CD8+ T cells against brain tumors and mediate checkpoint blockade-induced survival benefit. (gpdunnlab.com)
  • Hepatocellular carcinoma (HCC) is a moderately mutated tumor, where the neoantigen repertoire has not been investigated. (unav.edu)
  • Blocking both interactions increased the number of tumor-infiltrating CD8 + T cells, including CD8 + T cells specific for the tumor neoantigen M86. (acir.org)
  • In the context of the clinical translation of immune tolerance strategies, we discuss the significant challenge that is embodied by the fact that targeted pathway modulators may have opposing effects on tolerance based on their impact on effector vs regulatory T-cell biology. (umn.edu)
  • These coexpression factors (SASH3 and CD53) can be used to classify tumor purity phenotypes and to predict clinical outcomes. (hindawi.com)
  • Despite increased focus on the clinical relevance of dormant metastatic disease, our understanding of dormant niches, mechanisms underlying emergence from dormancy, and the immune system's role in this phenomenon, remains in its infancy. (nature.com)
  • The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient. (nature.com)
  • The clinical success of immune checkpoint inhibitors has dramatically changed outcomes for patients across cancer types. (biomedcentral.com)
  • 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)
  • Tumour-specific expression of MHC-I and MHC-II has been associated with improved patient survival in most clinical studies. (portlandpress.com)
  • However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. (explorationpub.com)
  • Project 1 will conduct a clinical trial to evaluate a peptide vaccine targeting Tumor-Associated Antigens (TAAs), given with an adjuvant poly-ICLC (Hiltonol). (cancer.gov)
  • Immunotherapies continue as an active and promising area of investigation, but clinical success has been limited by GBM's surprisingly potent capacities for eliciting severe local and systemic immune dysfunction, including profoundly low circulating T cell counts. (cancer.gov)
  • Recently the research findings from the laboratory and in experimental animals are translated to an early clinical study in which cancer patients are injected with and experimental tumor-specific peptide-conjugate vaccine. (universiteitleiden.nl)
  • Nonetheless, immune tolerance remains the holy grail of transplantation immunology and clinical transplantation. (medscape.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)
  • A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. (stanford.edu)
  • In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. (wikipedia.org)
  • This reduces the proliferation of antigen-specific T-cells in lymph nodes, while simultaneously reducing apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells) - further mediated by a lower regulation of the gene Bcl-2. (wikipedia.org)
  • this molecule was renamed as PD-L1 because it was identified as a ligand of PD-1 Several human cancer cells expressed high levels of B7-H1, and blockade of B7-H1 reduced the growth of tumors in the presence of immune cells. (wikipedia.org)
  • PD-L1 binding to PD-1 also contributes to ligand-induced TCR down-modulation during antigen presentation to naive T cells, by inducing the up-regulation of the E3 ubiquitin ligase CBL-b. (wikipedia.org)
  • Type I interferons can also upregulate PD-L1 on murine hepatocytes, monocytes, DCs, and tumor cells. (wikipedia.org)
  • The changes of immune cells and cytokines in vitro and in vivo were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA). (biomedcentral.com)
  • Niraparib upregulated membrane PD-L1 and total PD-L1 expression in ovarian cancer cells and had a synergistic effect with PD-L1 blockade in vivo. (biomedcentral.com)
  • In vivo and vitro, Niraparib can also increase the proportion of T cells and combined with PD-L1 blockade could further enhance the effect. (biomedcentral.com)
  • Our results showed that Niraparib could upregulate PD-L1 expression, but did not impair the function of immune cells, especially CD8 + T cells. (biomedcentral.com)
  • Interestingly, Niraparib enhanced the proportion and function of T cells via activation of the innate immune response pathway. (biomedcentral.com)
  • However the function of VEGF over the biology of immune system cells especially Tregs has just been recently valued (2). (opioid-receptors.com)
  • Engagement of PD-1 on T cells with PD-L1 on tumor cells downregulates antitumor T cell replies (3 4 Upregulation of PD-L1 by neoplastic cells enables tumors to flee the antitumor effector T cell replies. (opioid-receptors.com)
  • Nevertheless little information is normally on the comparative contribution of PD-1 inhibitory pathways towards the dampened antitumor T cell replies or the influence of PD-1 blockade on reinvigoration of fatigued T cells in HCC sufferers. (opioid-receptors.com)
  • Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. (elifesciences.org)
  • The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. (elifesciences.org)
  • Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. (aacrjournals.org)
  • More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which were stable or increased by the addition of rapamycin, but suppressed when PD901 was added. (aacrjournals.org)
  • Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. (aacrjournals.org)
  • One focus of the Powell lab is on the generation/isolation high avidity, tumor-reactive T cells from heterogenous tumor infiltrating lymphocyte populations in traditionally "non-immunogenic" cancers utilizing novel T cell capture techniques, and to deeply examine the characteristics and function of these immune cells. (upenn.edu)
  • This serves as a guidepost for rationally designing new combination checkpoint therapies, downstream T cell receptor (TCR) isolation, cancer antigen identification and molecular characterization of naturally occurring tumor-reactive T cells in human cancer. (upenn.edu)
  • Another field of study is the de novo generation of tumor-reactive T cells through genetic engineering methods. (upenn.edu)
  • We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). (bmj.com)
  • Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. (bmj.com)
  • Finally, these uncertified memory cells were not protective against a B16 tumor challenge. (bmj.com)
  • Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming. (bmj.com)
  • However, these immunotherapeutic approaches are hampered by the tumor-promoting nature of myeloid cells, including monocytes, macrophages, and neutrophils. (frontiersin.org)
  • Despite the arsenal of defense strategies against foreign invaders, myeloid cells succumb to the instructions of an established tumor. (frontiersin.org)
  • In this review, we discuss how rudimentary defense mechanisms deployed by myeloid cells can promote tumor progression. (frontiersin.org)
  • Although tumor-promoting functions have been attributed to other granulocytes, like eosinophils ( 17 ), basophils ( 18 ) and mast cells ( 19 ), further research is required to fully elucidate their role in cancer, as antitumoral roles have also been described ( 20 , 21 ). (frontiersin.org)
  • Nevertheless, the majority of scientific discoveries points toward a more tumor-supporting role for myeloid cells in the TME. (frontiersin.org)
  • These nontumor cells dilute the tumor purity in lung cancer tissues. (hindawi.com)
  • In addition to tumor cells, there are also other components such as stromal cells, inflammatory cells, vasculature, and the extracellular matrix [ 1 ]. (hindawi.com)
  • We are now aware that lung cancer tissues are rich in nontumor cells, of which stromal cells significantly regulate tumor proliferation, invasion, and angiogenesis [ 6 ]. (hindawi.com)
  • With the development of bioinformatics in recent years and the acquisition of open lung cancer cohorts, it becomes possible to evaluate tumor purity content in the samples according to the estimated infiltration of stromal and immune cells ESTIMATE algorithm [ 7 ]. (hindawi.com)
  • PD-L1 overexpression results in increased resistance of tumor cells to CD8 T cell mediated lysis. (bioxcell.com)
  • Predicted epitopes were synthesized in the form of synthetic long peptides and tested in immune system sensitization assays involving unfractionated peripheral blood mononuclear cells (PBMC). (ndltd.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)
  • Rosenberg and colleagues review evidence suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans. (nature.com)
  • The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function. (nature.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)
  • Their expression in tumour cells is modulated by a complex interplay of genomic, transcriptomic and post translational factors involving multiple intracellular antigen processing pathways. (portlandpress.com)
  • Ongoing research investigates mechanisms invoked by cancer cells to abrogate MHC-I expression and attenuate anti-tumour CD8 + cytotoxic T cell response. (portlandpress.com)
  • The discovery of MHC-II on tumour cells has been less characterized. (portlandpress.com)
  • This review provides a comprehensive overview of physiologically conserved or novel mechanisms utilised by tumour cells to reduce MHC-I or MHC-II expression. (portlandpress.com)
  • 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)
  • The effects of antibody-mediated blockade of CD1d on DC number and phenotype, priming of anti-tumor T cells, and tumor response to treatment with local radiotherapy and anti-CTLA-4 antibody were evaluated. (biomedcentral.com)
  • 0.05), suggesting the selective elimination of DCs cross-presenting tumor-associated antigens by iNKT cells. (biomedcentral.com)
  • Consistently, priming of T cells to a tumor-specific CD8 T cell epitope in mice treated with radiotherapy and anti-CTLA-4 or anti-CD137 was markedly enhanced in iNKT −/− compared to WT mice. (biomedcentral.com)
  • Here we describe a novel mechanism of tumor immune escape mediated by iNKT cells that limit priming of anti-tumor T cells by controlling DC in tumors and draining lymph nodes. (biomedcentral.com)
  • Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)
  • This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. (explorationpub.com)
  • These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. (explorationpub.com)
  • LECs are presumably the first cells that come into direct contact with peripheral antigens, cytokines, danger signals, and immune cells travelling from peripheral tissues to lymph nodes. (jci.org)
  • Immunologists recognized the importance of lymphatic vessels as channels for leukocyte trafficking from peripheral sites to their draining LNs ( 4 - 6 ), and as conduits for soluble antigens that can be taken up directly by LN-resident B cells and immature DCs ( 7 - 10 ), which help regulate the kinetics of antigen presentation. (jci.org)
  • Lymphatic endothelial cells (LECs) themselves have been shown to play active roles in controlling their transport functions and in directly communicating with immune cells to modulate their immediate and downstream functions. (jci.org)
  • While we particularly focus on LEC interactions with DCs and T cells, we also highlight features that support immune regulation, including the structure and function of lymphatic vessels and the compartmentalization of the LN stroma, which help control the manner in which LECs can interface with immune cells. (jci.org)
  • The lymphatic vessels and secondary lymphoid organs (SLOs) are arranged in a manner that optimizes interactions among antigens, APCs, and innate and adaptive effector cells. (jci.org)
  • This treatment utilizes a patient's own immune system to recognize and attack cancer cells. (aacr.org)
  • These strategies rely on the isolation of T cells, which are either genetically modified to target tumor-specific antigens or are expanded from an endogenous population that recognizes tumor neoantigens. (aacr.org)
  • Unlike CAR T-cell therapy or TCR therapy, which modifies T cells taken from the blood, TIL therapy utilizes T cells that have infiltrated the tumor stroma, which requires a tumor biopsy. (aacr.org)
  • Tumor-specific T cells are identified, expanded, and infused into the lymphodepleted patient, where they can help mediate tumor regression. (aacr.org)
  • To improve this therapeutic strategy, Rosenberg and colleagues developed a method to identify the exact antigens that the T cells could recognize. (aacr.org)
  • Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. (mdpi.com)
  • The observation that the immune system can also attack malignant cells has been known for many years but the cellular and molecular mechanisms have become clear in the last decades. (universiteitleiden.nl)
  • Therapeutic vaccination has the major advantage that the induced immune response selectively attacks tumors while leaving the healthy cells untouched. (universiteitleiden.nl)
  • We use established preclinical models, new preclinical models we have developed, and patient-derived tissue and cells to address what T cells recognize and how antigen is presented. (gpdunnlab.com)
  • In these same APC subsets, we identified a tumor-specific fluorescent metabolite of 5-aminolevulinic acid, which fluorescently labeled tumor cells during fluorescence-guided GBM resection. (gpdunnlab.com)
  • Single-cell transcriptomics and functional assays defined a high ratio of CD8(+) T cells versus T-reg cells as a predictor of response to immune checkpoint blockade (ICB). (unav.edu)
  • This class of personalized therapies involves collecting immune cells from an individual, engineering them to recognize and kill cancer cells, before culturing, and reintroducing them into the same individual. (technologynetworks.com)
  • Endogenous biomolecules (such as lactate dehydrogenase) or previously added exogenous labels (such as the radioisotope 51Cr) that leak into the media are then measured as an indirect readout of the damage caused by effector cells. (technologynetworks.com)
  • Tumor growth diminished 5 times and tumor weight reduced 50-80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. (oncotarget.com)
  • The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. (oncotarget.com)
  • The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo . (oncotarget.com)
  • One of the new emerging mechanisms associated with the progression of clear cell renal cell carcinoma (ccRCC) and other tumors is the immune checkpoint pathway, which consists of cellular interactions that prevent excessive activation of T cells under normal conditions. (oncotarget.com)
  • As an evasion mechanism, many tumors are able to stimulate the expression of immune checkpoint molecules, resulting in an exhausted phenotype of T cells that cannot restrain tumor progression [ 1 ]. (oncotarget.com)
  • Consistent with in vitro observations, in mice with PD-L1-deficient MC38 colorectal tumors where only host cells were the source of PD-L1, antibody blockade of both PD-1/PD-L1 and PD-L1/B7-1 interactions reduced tumor growth, while blocking only PD-L1/B7-1 interactions slightly accelerated tumor growth due to an increased availability of PD-L1. (acir.org)
  • Analysis of the tumor-infiltrating myeloid populations at days 3, 7, and 14 post tumor inoculation revealed that the majority of myeloid cells were macrophages, which far outnumbered cross-presenting dendritic cells (DCs). (acir.org)
  • Most myeloid cells within tumors and tumor-draining lymph nodes expressed PD-L1 without co-expressing B7-1 (but still expressing B7-2, which does not interact in cis with PD-L1), thus leaving plenty of PD-L1 free to interact with PD-1 on T cells. (acir.org)
  • Most intratumoral PD-L1 + myeloid cells were macrophages (~75%), while cross-presenting DCs accounted for less than 2% of this population by day 14 post tumor inoculation. (acir.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)
  • Animal studies have shown that LAK cells are more effective against cancer cells than are the original endogenous T cells, presumably because of their greater number. (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)
  • Tumor Antigens 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)
  • In contrast to TCR T cells, CAR T cells recognize only relatively large proteins on the surface of 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)
  • T-cell engagers are bispecific antibodies that recruit cytotoxic T cells to kill tumor cells. (msdmanuals.com)
  • The most frequently used engagers are antibodies targeting one tumor antigen and one molecule on T cells (mostly CD3). (msdmanuals.com)
  • CD1d blockade restored the number of DC in WT mice, improved T cell priming in draining lymph nodes and significantly enhanced response to treatment. (biomedcentral.com)
  • We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor antigen. (gpdunnlab.com)
  • Niraparib could modulate the immune response via the activation of the cGAS/STING pathway, and combination with PD-L1 blockade could further enhance the effect. (biomedcentral.com)
  • Using GSEA analysis, we found that the antigen processing and presentation pathway were related to the five tumor coexpressed genes mentioned above. (hindawi.com)
  • For those who are ineligible for cisplatin-based regimens or experience progression of disease, in 2016-2017 the United States Food and Drug Administration approved five monoclonal antibodies that achieve immune checkpoint blockade by targeting the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) pathway. (iospress.com)
  • This was regulated by the hedgehog pathway (Gli2, Bmi1, and Sox 2) to promote tumour initiation and maintenance [41]. (globaltechbiz.com)
  • Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. (aacrjournals.org)
  • In vivo antibody depletion revealed a CD8 T-cell-dependent, and not NK cell-dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell-mediated antibody-dependent cellular cytotoxicity. (aacrjournals.org)
  • inhibition of AGE generation with aminoguanidine, macrophage depletion with clodronate liposomes, and antibody-based blockade of Il-1 and Tlr4 attenuated diabetes-induced retinal expression in mice. (ece-inhibitor.com)
  • As binding of miRNAs to a target mRNA may result in an airway inflammatory disease closely correlates with either mRNA degradation or inhibition of protein immune regulation, more and more evidences suggest translation.1 More than 2000 miRNAs have been discovered in humans. (cdc.gov)
  • Malignant primary brain tumors, like glioblastoma (GBM), are the most frequent cause of cancer death in children and young adults and account for more deaths than cancer of the kidney or melanoma. (cancer.gov)
  • Building on the Duke Brain Tumor Program's longstanding focus on development, refinement, and testing of immunotherapies to treat low-grade gliomas and GBM, the Duke SPORE in Brain Cancer continues work to develop new or improve existing therapies to improve the life of patients with primary malignant brain tumors. (cancer.gov)
  • Brain tumors typically begin as slow growing low grade gliomas (LGGs) that transform in almost all cases to a universally lethal high grade glioma (HGGs) within 10 years. (cancer.gov)
  • Using immunology and genomics tools, we study how the immune response to brain tumors happens. (gpdunnlab.com)
  • Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. (aacrjournals.org)
  • Treating tumor-bearing PD-L1 ΔDC mice with anti-PD-L1 antibodies that blocked either only the PD-L1/B7-1 interactions or both the PD-L1/B7-1 interactions and PD-L1/PD-1 interactions did not further enhance tumor control. (acir.org)
  • The effect of Niraparib and PD-L1 blockade in ovarian cancer progression was investigated in vivo. (biomedcentral.com)
  • Functionally, the OX40hiGITRhi subset is the most highly suppressive ex vivo, and its higher representation among total TIL-Treg correlated with resistance to PD-1 blockade. (bvsalud.org)
  • by contrast, PD-L1 removal increases phagocytosis in vivo , decreases tumour burden and increases survival of mice. (nature.com)
  • Vaccination using optimized strategies may increase response rates to immune checkpoint inhibitors (ICI) in some tumors. (unav.edu)
  • As an alternative, T cell receptor (TCR)-engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma. (gpdunnlab.com)
  • Altogether, the myeloid compartment in the TME is heterogenous and varies across tumor types, individuals and tumor stage ( 23 ). (frontiersin.org)
  • Interestingly, however, mature DCs in NSCLC tumors had the highest level of PD-L1 (and B7-1) expression on a per cell basis among intratumoral myeloid populations. (acir.org)
  • However, the effects of Niraparib, one of the poly (ADP) ribose polymerase (PARP) inhibitors, on the immune response remains unclear. (biomedcentral.com)
  • However, the interactions between PARP inhibitors and the immune system as well as the underlying molecular mechanisms, remain unknown. (biomedcentral.com)
  • Ferry A. Ossendorp is Professor Molecular Vaccin Biology and head of the Tumor Immunology group in the department Immunology of the Leiden University Medical Centre. (universiteitleiden.nl)
  • For more than 25 years Ferry Ossendorp is investigating the immune system and cancer and is now head of the Tumor Immunology Group. (universiteitleiden.nl)
  • These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. (elifesciences.org)
  • Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. (aacrjournals.org)
  • The Powell Lab is actively investigating and translating the application of immune-based therapy for cancer, with emphasis on gynecologic cancers. (upenn.edu)
  • Tumor purity plays an essential role in the immune response to lung cancer. (hindawi.com)
  • At present, the biological processes related to the purity of lung cancer tumors remains unclear. (hindawi.com)
  • A lung cancer tumor purity correlated coexpression network was determined. (hindawi.com)
  • 2018). "Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme" Nat Biotechnol 36(8): 758-764. (bioxcell.com)
  • Drugs that mobilize our immune systems against cancer are dramatically improving care for many people, and research is rapidly moving ahead in the lab and the clinic. (nature.com)
  • The discovery and development of novel treatments that harness the patient's immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. (biomedcentral.com)
  • Evading immune destruction is one of the hallmarks of cancer. (portlandpress.com)
  • However, PD-1 blockade alone is not able to antagonize all resistance mechanisms and quite a proportion of cancer patients do not respond to this treatment (primary resistance), and some responders relapse after a period of response (acquired resistance) [ 4 ]. (oncotarget.com)
  • Ossendorp, F. & Cruz, L.J. (2023), Effective combination of liposome-targeted chemotherapy and PD-L1 blockade of murine colon cancer, Journal of Controlled Release 353: 490-506. (universiteitleiden.nl)
  • A similar PD-L1 expression distribution was observed in RNASeq data from human non-small cell lung cancer (NSCLC) tumors. (acir.org)
  • 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)
  • Neutrophils also contribute to tumor progression, yet establishing the difference between PMN-MDSCs and tumor-associated neutrophils (TAN) remains challenging ( 11 , 15 , 16 ). (frontiersin.org)
  • The most commonly used method for measuring immune cell‑mediated killing is the release assay, where effector cell‑mediated disruption of the target cell membrane results in leakage of its cytoplasmic contents into the culture medium. (technologynetworks.com)
  • In the demyelinating form, segmental demyelination of peripheral nerves is thought to be immune mediated and both humoral and cell-mediated immune mechanisms have been implicated. (medscape.com)
  • Rosenberg is beginning to develop a library of TCRs that can recognize shared mutations in the hope of utilizing them for TCR T-cell therapy for patients across a variety of tumor types, especially those with common epithelial cancers. (aacr.org)
  • While the different phases of an immune response are well known, the mechanisms underlying the formation of protective memory are not well understood. (bmj.com)
  • Fig. 1: Proposed mechanisms of quiescence and immune evasion in dormancy. (nature.com)
  • Since the vast majority of the morbidity and mortality occurs in immune-naïve African children less than five years of age, with SMA as the primary manifestation of severe disease, this review will focus primarily on the innate immune mechanisms that govern malaria pathogenesis in this group of individuals. (ijbs.com)
  • Immunotherapeutics Immunotherapeutic agents use or modify immune mechanisms. (msdmanuals.com)
  • This early phase trial will inform a subsequent larger trial, potentially combining the P30-EPS multi antigen vaccine with a clinically available bi-specific antibody (CDX-527) that combines a CD27 agonist antibody (αCD27) with an anti-PD-L1 antibody (αPD-L1). (cancer.gov)
  • Sera from ladies with and without histories of UTI have been tested for antibody levels to vaccine antigens. (morainetownshipdems.org)
  • The local antibody delivery led to marked immune checkpoint blockade. (oncotarget.com)
  • 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)
  • We further hypothesized that epitope prediction strategies which seek to identify pan- or highly promiscuous-HLA binding epitopes would reduce the number of potential candidates and be more likely to accurately identify high-priority tumor Ag epitopes. (ndltd.org)
  • This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. (elifesciences.org)
  • CDX-527 induces greater T cell stimulation, PD-1/PD-L1 axis checkpoint blockade, and potentiate anti-tumor immune activity. (cancer.gov)
  • VEGF was originally defined as a tumor-secreted aspect that elevated vascular permeability marketed angiogenesis and therefore facilitated tumor development. (opioid-receptors.com)
  • Folkman, J. Tumor angiogenesis: therapeutic implications. (nature.com)
  • antigens that can separately protect experimentally infected mice from colonization of the bladder and/or kidneys by UPEC when given intranasally with cholera toxin (CT) as an adjuvant. (morainetownshipdems.org)
  • We shown for all four vaccine antigens that antigen-specific serum IgG represents a strong correlate of safety in vaccinated mice. (morainetownshipdems.org)
  • In animals bearing PD-L1-deficient MC38 tumors, mice with total PD-L1 knockout (KO) controlled tumor growth better than wild-type (WT) mice, as observed previously. (acir.org)
  • PD-L1 ΔDC mice controlled tumors as effectively as PD-L1 KO mice, while PD-L1 ΔMF mice were not effective, reducing tumor growth only slightly compared to WT controls. (acir.org)
  • Similar results were observed in mice bearing PD-L1-sufficient tumors. (acir.org)