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  • Head and Neck Squamous Cell Carc
  • Head and neck squamous cell carcinoma (HNSCC) of the oral cavity, pharynx and larynx combined account for 60,000 new cases of malignant tumors and 12,000 tumor related deaths annually in the USA, with comparable numbers in Europe [ 1 - 3 ]. (oncotarget.com)
  • neoantigens
  • Mutation-derived neoantigens represent an important class of tumour-specific, tumour rejection antigens, and are attractive targets for TCR gene therapy of cancer. (springer.com)
  • Therefore, neoantigens represent an important class of tumour-specific, tumour rejection antigens, which can be targeted by neoantigen-specific T cell receptors (TCRs). (springer.com)
  • A second class of potential cancer rejection antigens is formed by peptides that are entirely absent from the normal human genome, so-called neoantigens. (sciencemag.org)
  • For virus-associated tumors, such as cervical cancer and a subset of head and neck cancers, epitopes derived from viral open reading frames also contribute to the pool of neoantigens. (sciencemag.org)
  • We will describe the current methods and techniques of detection as well as the structural requirements for neoantigens that are needed for their recognition by T cells and for tumor destruction. (frontiersin.org)
  • In NSCLC patients, CD8 + T cells reactive to these clonal neoantigens were detected infiltrating tumors, and their presence was associated with enhanced sensitivity to anti-PD1 mAb ( 9 ). (aacrjournals.org)
  • The main paradigm behind the development of cancer vaccines rests on the assumption that if the immune system is stimulated to recognize neoantigens, it may be possible to elicit the selective destruction of tumor cells. (beds.ac.uk)
  • As we move from vaccines targeting 'shared' tumor antigens to a more 'personalized' medicine approach, in silico strategies are needed to first identify, then determine which somatic alterations provide the optimal neoantigens for the vaccine design. (beds.ac.uk)
  • Ideally, an optimal strategy would intake mutation calls from massively parallel sequencing data comparisons of tumor to normal DNA, identify the neoantigens in the context of the patient's HLA alleles, and parse out a list of optimal peptides for downstream testing. (beds.ac.uk)
  • rejection
  • We confirmed the validity of the in vivo model by showing that the melan-A-specific (MART-1-specific) TCR DMF5 induces rejection of tumors expressing analog, but not native, MART-1 epitopes. (jci.org)
  • On theoretical grounds, such cancer rejection epitopes may be derived from two classes of antigens. (sciencemag.org)
  • A first class of potential cancer rejection antigens is formed by nonmutated proteins to which T cell tolerance is incomplete-for instance, because of their restricted tissue expression pattern. (sciencemag.org)
  • vivo
  • Wild-type MC38 cells outcompeted PD-L1-deleted MC38 cells in vivo , demonstrating tumor PD-L1 confers a selective advantage. (rupress.org)
  • primary tumors
  • To assess whether MAGE expression increases with metastasis or recurrence, a tissue microarray (TMA) of 552 primary tumors (PT), 219 LNM and 75 RD was evaluated by immunohistochemistry for MAGE antigens using three monoclonal antibodies to multiple MAGE family members. (oncotarget.com)
  • cells
  • SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade. (nih.gov)
  • We show that the immunodominant SPAS-1 epitope SNC9-H(8) arose from a point mutation in one allele of the gene in TRAMP tumor cells, and that immunization with dendritic cells pulsed with SNC9-H(8) peptide resulted in protection against TRAMP-C2 tumor challenge. (nih.gov)
  • A ) The tumor specificity of the T cell line was determined by specific IFN-γ production in response to TRAMP-C2, MC38, B16BL6, or EL4 target cells. (nih.gov)
  • Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8 + T cells without the need for tumor antigen characterization. (springer.com)
  • However, the nature of the antigens that allow the immune system to distinguish cancer cells from noncancer cells has long remained obscure. (sciencemag.org)
  • In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells. (frontiersin.org)
  • PD-1 is expressed on surface of activated T cells as an inhibitory receptor ( 2 ), while its ligands PD-L1 and PD-L2 are mainly expressed in antigen-presenting cells and tumor cells ( 3 , 4 ). (frontiersin.org)
  • However, most studies on PD-1 expression have focused on immune cells, rendering its potential expression and functions in tumor cells remaining largely unclear. (frontiersin.org)
  • Conventional chemotherapies target tumors but also dividing cells in healthy organs and are therefore frequently associated with significant toxicity. (frontiersin.org)
  • We showed that an agonistic anti-CD40 mAb converted PD1 hi T cells into PD1 lo T cells, reversing phenotypic T-cell exhaustion and allowing the anti-PD1 refractory tumors to respond to anti-PD1 therapy. (aacrjournals.org)
  • Given that PD1 expression is mainly found on intratumor T cells, it is anticipated that the lack of tumor-infiltrating CD8 + T cells is one of the major reasons for anti-PD1 insensitivity ( 11 ). (aacrjournals.org)
  • CTL-associated antigen 4 (CTLA4) is a costimulatory molecule expressed on activated T cells that delivers an inhibitory signal to these T cells. (aacrjournals.org)
  • CTL-associated antigen 4 (CTLA4) signaling provides negative feedback to activated T cells, thereby dampening an immune response ( 1 , 2 ). (aacrjournals.org)
  • These effects are presumably mediated by preexisting tumor-specific T cells that were primed by endogenous tumor-derived antigens and are receptive to CTLA4 blockade. (aacrjournals.org)
  • Cancer cells can evade detection and eradication by the immune system by reducing antigen expression, secreting immune-suppressive cytokines, or upregulating inbuilt inhibitory signals. (biomedcentral.com)
  • Innate immune response includes dendritic cells, which are involved in antigen presentation, neutrophils and phagocytes, and activation of the complement system. (biomedcentral.com)
  • A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. (upenn.edu)
  • Cytokine analysis of tissues from brain tumor-bearing mice detected elevated TGF-β secretion from microglia and in the serum and TGF-β signaling blockade reversed tolerance of tumor antigen-directed CD8 T cells. (aacrjournals.org)
  • Results: CNS melanomas were more tolerogenic than equivalently progressed tumors outside the CNS as antigen-specific CD8 T cells were deleted and exhibited impaired cytotoxicity. (aacrjournals.org)
  • Recent studies have also shown an important maturation role for FcγR expression on mouse antigen-presenting cells, including DCs ( 13 ). (pnas.org)
  • Recent preclinical data indicate that these mutated proteins, upon processing and presentation in the context of MHC molecules expressed by antigen-presenting cells, can be recognized as 'non-self' by the immune system. (beds.ac.uk)
  • Vaccines incorporate these neoantigen peptides with the aim of enhancing the immune system's anti-tumor activity by selectively increasing the frequency of specific CD8+ T cells, and hence expanding the immune system's ability to recognize and destroy cancerous cells. (beds.ac.uk)
  • anti-PD1 therapy
  • Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS). (aacrjournals.org)
  • antitumor
  • Promising antitumor activity without detrimental side effects, the advent of targeted therapies as a novel class of more tumor-selective oncology drugs initially raised a lot of enthusiasm. (frontiersin.org)
  • mutation
  • Here, we present a flexible, streamlined computational workflow for identification of p ersonalized V ariant A ntigens by C ancer Seq uencing (pVAC-Seq) that integrates tumor mutation and expression data (DNA- and RNA-Seq). (beds.ac.uk)
  • refractory
  • However, most patients do not show durable remission, and some tumors have been completely refractory to response with checkpoint blockade, highlighting the requirement of understanding the role of PD-1/PD-L1 axis during the oncogenic and metastatic processes ( 7 - 9 ). (frontiersin.org)
  • mice
  • B ) Mouse Spas-1 expression in normal versus tumor prostate: the level of Spas-1 expression was determined in a panel of normal prostates and primary TRAMP tumors from 21- and 27-week-old mice. (nih.gov)
  • immunization
  • On day 20 after immunization the antigen-specific Th1/Th17 response was evaluated by enzyme-linked immunospot (ELISPOT) in spleen and central nervous system (CNS). (ox.ac.uk)