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Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [RNA-Seq]

ABSTRACT: IL-2/IL-15/IL-21-expanded TILs achieved complete tumor regression in a hypermutated glioblastoma patient, overcoming the immunosuppressive microenvironment. This case highlights a novel approach for treating gliomas using tailored adoptive cell therapy strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285281 | GEO | 2025/12/02

REPOSITORIES: GEO

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Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [WES]

Project description:IL-2/IL-15/IL-21-expanded TILs achieved complete tumor regression in a hypermutated glioblastoma patient, overcoming the immunosuppressive microenvironment. This case highlights a novel approach for treating gliomas using tailored adoptive cell therapy strategies.

2025-12-02 | GSE285283 | GEO

Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [TCR]

2025-12-02 | GSE285282 | GEO

Evaluation of Tumor Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Project description:Tumor infiltrating lymphocytes (TILs) play a significant role in the tumor microenvironment in high-grade serous ovarian cancer (HGSOC). To better understand the interactions and functions of TILs in HGSOC progression, we performed proteogenomic profiling of TILs in 65 tumors collected from 12 HGSOC patients.

2024-03-15 | PXD045710 | Pride

Microbial Peptides Activate Tumor-Infiltrating Lymphocytes in Glioblastoma

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

Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [WES]

Project description:Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [WES]

| PRJNA1202161 | ENA

Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [TCR]

Project description:Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [TCR]

| PRJNA1202146 | ENA

Expression data from FACS-sorted CD8+BTLA+ vs CD8+BTLA- Human Tumor-infiltrating Lymphocytes in Metastatic Melanoma

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

Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [RNA-Seq]

Project description:Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma [RNA-Seq]

| PRJNA1202144 | ENA

PD-1 blockade-unresponsive human tumor-infiltrating CD8+ T cells are marked by loss of CD28 expression and rescued by IL-15

Project description:Blockade of programmed death-1 (PD-1) reinvigorates exhausted CD8+ T cells, resulting in tumor regression in cancer patients. Recently, reinvigoration of exhausted CD8+ T cells following PD-1 blockade was shown to be CD28-dependent in mouse models. Herein, we examined the role of CD28 in anti-PD-1-induced human T-cell reinvigoration using tumor-infiltrating CD8+ T cells (CD8+ TILs) obtained from non-small cell lung cancer patients. Single cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8+ TILs. Furthermore, we found that human CD28+CD8+, but not CD28–CD8+ TILs, responded to PD-1 blockade irrespective of B7/CD28 blockade, indicating that CD28 co-stimulation in human CD8+ TILs is dispensable for PD-1 blockade-induced reinvigoration, and loss of CD28 expression rather serve as a marker of anti-PD-1-unresponsive CD8+ TILs. Transcriptionally and phenotypically, PD-1 blockade-unresponsive human CD28–PD-1+CD8+ TILs exhibited characteristics of terminally exhausted CD8+ T cells with low TCF1 expression. Notably, CD28–PD-1+CD8+ TILs had preserved machinery to respond to IL-15, and IL-15 treatment enhanced proliferation of CD28–PD-1+CD8+ TILs as well as CD28+PD-1+CD8+ TILs. Taken together, we demonstrate loss of CD28 expression as a marker of PD-1 blockade-unresponsive human CD8+ TILs with TCF1– signature and provide mechanistic insights into combining IL-15 with anti-PD-1.

2020-05-01 | GSE145896 | GEO

Human CD28+/- tumor infiltrating lymphocytes gene expression

Project description:This analysis reveals the different gene expression profiles between human melanoma tumor infiltrating lymphocytes subsets CD8+CD28+ and CD8+CD28-. Adoptive cell therapy (ACT) is an effective approach that removes tumor-infiltrating lymphocytes (TILs) from this suppressive tumor microenvironment and expands and activates CD8+ and CD4+ T cells in vitro, differentiating them into potent anti-tumor effector cells that can be re-introduced back into patients. One of the key problems that may limit tumor regression and long-term durable clinical responses in ACT is the persistence of TILs following infusion. Our study has indicated that ex vivo expanded TILs to be hypo-responsive to peptide re-stimulation, manifested in slow entry into cell cycle and increased apoptosis. Phenotypic and functional analysis using a number of different T-cell differentiation markers found that CD28 was markedly down-modulated in post-REP cells, while CD27 and CD57 levels showed no statistically-relevant changes in expression. Here on a global gene expression level, microarray gene chip analysis of sorted CD8+CD28+ and CD8+CD28- post-REP TILs revealed a number of key differences in their gene expression profiles; notably, an increase in KIR family member expression, loss of p53-binding proteins, and lower CD127/IL-7Ra gene expression found in the CD28- population. On top of advancing T cell phenotype, reactivation and memory, this set of data may also provide insight for ACT clinical protocol optimization to improve TIL response in vivo.

2009-06-10 | GSE16517 | GEO

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