Similar Datasets
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: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:B7S1 negatively regulates T cells and its expression correlates with poor prognosis of cancer patients. In order to understand how B7S1 signaling contributes to dysfunction of CD8+ T cell in the TME, we conducted transcriptional analysis of OVA-specific CD8+ TILs and different TIL subsets from E.G7-bearing WT and B7S1 KO mice (Day 21).
2018-04-03 | GSE110249 | GEO
Project description:Naive B6.2.16 CD8 T cells (>85% pure) were isolated from the lymph nodes (LN) of female RAG1-deficient B6.2.16 mice. B6.2.16 CD8 T cell effectors were generated by culturing splenocytes from female RAG1-deficient B6.2.16 mice with HY peptide for 4 d and adoptively transferred into female RAG1-deficient mice. After 200 d, memory B6.2.16 CD8 T cells (>80% pure) were recovered from the spleens and LNs by magnetic bead sorting. Sample proRNA from naïve and memoryB6.2.16 CD8 T cells was isolated using Trizol(r) Reagent and used to make cRNA for hybridization according to Affymetrix protocols. Keywords: other
2004-08-05 | GSE1578 | GEO
Project description:CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.
2021-09-14 | GSE184053 | GEO
Project description:CD8+ T cells isolated from HCC tissue were divided into three groups: PD1-TIM3- CD8+ TILs, exhibiting full effector function; PD1-intTIM3+ CD8+ TILs, exhibiting partial exhaustion; and PD1-hiTIM3+ CD8+ TILs, exhibiting severe exhaustion, as reflected by the differences in their ability to produce effector cytokines respectively. Transcriptome sequence analysis was performed to investigate the gene expression profile was performed.
2019-12-31 | E-MTAB-7278 | biostudies-arrayexpress
Project description:Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact.
2016-09-07 | GSE85947 | GEO
Project description:It has been shown that tumor infiltrating immune cells have a profound impact on the outcome of FL. To find mechanisms whereby TILs are altered gene expession analysis of highly pure TILs were performed. The study is composed of 4 groups, FL CD4 (n=12), FL CD8 (n=9), Tonsil CD4 (n=7) and Tonsil CD8 (n=7). All FL patients were treatment naive. Cells were flowsorted from cryopreserved single cell suspensions and purity of cells were at least 95%.
2013-02-07 | E-GEOD-27928 | biostudies-arrayexpress
Project description:To decipher the molecular mechanism of NFAT5 KO CD8 T cells, we performed RNA sequencing on sorted P14 CD8 TILs seven days after CD8 T cell transfer.
2022-12-21 | GSE209680 | GEO
Project description:To decipher the molecular mechanism of NFAT5 or NFAT1 CA-RIT overexpressing CD8 T cells, we performed RNA sequencing on sorted P1A CD8 TILs seven days after CD8 T cell transfer.
2022-12-21 | GSE209682 | GEO