Ontology highlight
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PROVIDER: PRJNA754131 | ENA |
REPOSITORIES: ENA
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Project description:The immune system can recognize and respond to tumors. However there are some conditions in which the genetic instability and heterogeneity of tumor cells leads to the development of variants that can escape the immune system. T cells have infiltrated inside many tumors (Tumor Infiltrating Lymphocytes or TILs), but generally these TILs have lost their functional capacity and are unable to eliminate tumor cells. We developed a model of autochthonous melanoma in mice that recapitulates some aspects of inflammatory melanoma in humans. These include a systemic Th2/Th17-oriented chronic inflammation, recruitment of immunosuppressive myeloid cells and acquisition by TILs of an M-bM-^@M-^\exhaustedM-bM-^@M-^] phenotype characterized by expression of receptors for multiple inhibitory molecules. To address the molecular bases for the M-bM-^@M-^\exhaustedM-bM-^@M-^] TILs phenotype, we performed transcriptomic analyses on sorted CD8 or T cells from the induced melanomas. These transcriptomes were compared to those of naM-CM-/ve CD8 T cells and of CD8 T cells immunized with a virus. 10 samples, 3 replicates for controls (untreated and infected with AdP1A), 4 replicates for TILs CD8 from melanoma
2013-12-31 | E-GEOD-42824 | biostudies-arrayexpress
Project description:Discovery of patient-specific tumor antigens usually requires in vitro-expanded autologous tumor infiltrating lymphocytes (TILs), among which tumor antigen-specific T cells are however often rare, thus limiting sensitivity. We designed in vitro culture conditions to improve the identification of rare tumor antigen-specific CD8 TILs. This innovative yet accessible pipeline allows highly-sensitive identification of tumor antigens and cognate T cell receptors (TCRs), greatly improving the selection of candidates for personalized cancer vaccines and TCR-based cellular immunotherapies.
| EGAS00001005513 | EGA
Project description:Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells. We used microarrays to detail the differences in the global programme of gene expression between CD8+BTLA+ vs CD8+BTLA- TILs in order to understand the molecular basis of the clinical association. TILs were isolated by enzymatically digest the melanoma tumor fragments obtained from Stage IIIc/IV melanoma patients at M.D. Anderson Cancer Center. The TILs were expanded with high-dose IL-2 for two weeks prior to sorting by FACS (fluoresecence-activated cell sorter) for CD8+BTLA+ and CD8+BTLA- susbets. RNA was extracted from each sorted subsets and hybridized on Affymetrix microarrays
2013-01-03 | E-GEOD-43260 | biostudies-arrayexpress
Project description:Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Identification of genes associated with survival of metastatic melanoma Survival Analysis was performed using Statistical Analysis of Microarrays B D denotes same patient with multiple reccurences
2009-11-30 | E-GEOD-19234 | biostudies-arrayexpress
Project description:Identification and characterization of Tregs recognizing tumor-associated antigens.
| PRJDB11915 | ENA
Project description:Microbial organisms play key roles in numerous physiological processes in the human body and have recently been shown to modify the response to cancer radiotherapy and immune checkpoint inhibitors. Here, we demonstrate that HLA molecules of both glioblastoma tissues as well as tumor cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumor-infiltrating lymphocytes (TILs) recognize intratumoral microbiota. Indeed, bacterial peptides eluted from HLA-DR II molecules are recognized by both TILs, albeit weakly, and peripheral blood-derived memory CD4+ T cells, which, upon stimulation with bacterial peptides, also recognize several tumor antigens. Furthermore, using an unbiased antigen discovery approach for a TIL CD4+ T cell clone (TCC) we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumor antigens. These peptides were strongly stimulatory for bulk TILs and peripheral blood memory cells. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumor antigens.
2023-02-20 | PXD036811 | Pride
Project description:Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leukocyte antigens (HLA) on the surface of native tumor tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides. Most importantly, we identify peptide ligands presented on native tumor tissue samples harboring somatic mutations. Four of eleven mutated ligands prove to be immunogenic by neoantigen-specific T-cell responses. Moreover, tumor-reactive T cells with specificity for selected neoantigens identified by MS are detected in the patient`s tumor and peripheral blood. We conclude that direct identification of mutated peptide ligands from primary tumor material by MS is possible and yields true neoepitopes with high relevance for immunotherapeutic strategies in cancer.
2017-04-06 | PXD004894 | Pride
Project description:Dendritic cells loaded with tumor antigens induce cytotoxic T-cells which have been proved capable of killing both melanoma and breast cancer cells. Melanoma and colorectal cancer cells express some common antigens. Hence it is possible to use melanoma lysate to load the dendritic cells with tumor antigens similar to the antigens expressed by the patients’ colorectal cancer cells.
The patient receives 10 vaccinations with 14 days between each. The parameters for effect are changes in tumor/metastasis size measured with computed tomography (CT), decrease in serum concentration of carcinoembryonic antigen (CEA), performance status measured by the World Health Organization (WHO) criteria, and Quality of Life.
| 2027823 | ecrin-mdr-crc
Project description:Recent studies revealed that treatment resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptide derived from tumor-associated antigens (TAAs), thus identification of tumor-associated antigens (TAAs) expressed in CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires large scale of sample and it is challenging for CSCs/CICs. In this study, we established novel bladder CSC/CIC model from a bladder cancer cell line UM-UC-3 cells using ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH) high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immune deficient mouse. HLA ligandome analysis and gene expression (CAGE) using ALDHhigh clone cells revealed distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we identified GRIK2 derived antigenic peptide is specifically expressed in CSCs/CICs. GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressed UM-UC-3 cells and ALDHhigh clone cells indicating that GRIK2 peptide can be a novel target for bladder CSCs/CICs-targeting immunotherapy.
2021-10-01 | GSE166947 | GEO
Project description:Purpose: Characterization of the gene expression profile of CD8+ TILs (TRM vs. re-circulating) from 7 HGSOC
2022-03-07 | GSE194383 | GEO