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RNA Profiling in Patients' tumor infiltrating lymphocytes

ABSTRACT: Identifying tumor antigen-specific T cells from cancer patients has been a goal of tumor immunologists for several decades. Co-expression of CD103 and CD39 on CD8 TIL highly enriches for tumor-reactive T cells. CD39+CD103+ CD8 TIL have a distinct TCR repertoire compared to other CD8 TIL subsets and are clonally expanded within the tumor. They are highly enriched for tumor antigen recognition and efficiently killed autologous tumor cells. Patients with head and neck cancer whose CD8 TIL contained a higher frequency of CD39+CD103+ cells experienced a greater overall survival. This work describes a simple and effective method for detecting tumor-reactive CD8 TIL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE114944 | GEO | 2018/05/26

REPOSITORIES: GEO

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Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors

Project description:The subject of this study is the adoptive transfer of selected autologous tumor infiltrating lymphocytes (TIL) after in vitro expansion for the treatment of solid tumor malignancies. The TIL selection process is based on evidence showing that CD8+ TIL which co-express both CD39 and CD103 harbor the bulk of tumor-reactivity and that the remaining CD8 TIL is mainly composed of non-tumor reactive bystander cells. All of the expanded TIL that are produced (1-40 billion are expected) will be delivered in the form of a cell suspension to the participants by intravenous infusion. It is proposed that these selected TIL will produce a more potent and efficacious treatment of late-stage cancer.

| 63320 | ecrin-mdr-crc

Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis

Project description:Tumor-reactive CD8+ tumor infiltrating lymphocytes (TILs) represent a subtype of T cells that could recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated. In this study, we segregated tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer (CRC) patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirmed previous conclusion that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identified a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers (CD39 and CD103) being specifically demethylated. In addition, dynamic changes were observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor (TF) binding motif enrichment analysis identified several immune-related TFs, including three exhaustion-related genes (NR4A1, BATF and EGR2) and VDR, that potentially play important regulatory role in tumor-reactive CD8+ T cells. Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.

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CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [VDJ]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

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CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [scRNA]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

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CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [FB]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

2022-11-17 | GSE218259 | GEO

Profiling of lung tumor-infiltrating CD8 T cells according to their expression status of CD39

Project description:Human tumors are infiltrated by various immune cells, including CD8 T cells. CD8 T cells express unique receptors that can recognize peptides at the host’s cells, including tumor cells. After probing the antigen specificity of ex-vivo tumor-infiltrating CD8 T cells from human tumors, we hypothesized that expression of CD39 was correlated with tumor-specificity. The present experiment aims at better characterizing ex-vivo CD39+ vs CD39- CD8 T cells.

2018-05-17 | GSE113588 | GEO

Profiling of colorectal tumor-infiltrating CD8 T cells according to their expression status of CD39

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CD8+/CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients

Project description:We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T-cell distribution and functions, and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. Here we investigate the transcriptomic profil of these cell population, using PBMC cells as control.

2015-06-29 | E-MTAB-3266 | biostudies-arrayexpress

Molecular profile of tumor-specific CD8+ T cell hypofunction in cancer

Project description:Comparison of genome-wide mRNA expresson between tumor-infiltrating CD8+ T cells from the tumor (hypofunctional T cells) and periphery (functional T cells) Mechanisms of self-tolerance often result in CD8+ tumor-infiltrating lymphocytes (TIL) with a hypofunctional phenotype incapable of tumor clearance. Using a solid tumor model in mice, we found that CD8+ T cells became tolerized in less than 24 hours in an established tumor environment. To define the collective impact of pathways suppressing TIL function, we compared genome-wide mRNA expression of tumor-specific CD8+ T cells from the tumor and periphery. Notably, gene expression induced during TIL hypofunction more closely resembled self-tolerance than viral-exhaustion. Differential gene expression was refined to identify a core set of genes that defined hypofunctional TIL; these data comprise the first âmolecular profileâ of tumor-specific TIL that are naturally responding and represent a polyclonal repertoire. The molecular profile of TIL was further dissected to determine the extent of overlap and distinction between pathways that collectively restrict T cell functions. As suggested by the molecular profile of TIL, protein expression of inhibitory receptor LAG-3 was differentially regulated throughout prolonged late-G1/early-S phase of the cell cycle. Our data may accelerate efficient identification of combination therapies to boost anti-tumor function of TIL specifically against tumor cells. 4 samples, 3 biological replicates per group.

2016-04-03 | E-GEOD-79858 | biostudies-arrayexpress

Single-cell RNA-seq of human head and neck squamous cell carcinoma (HNSCC) to compare different tissue dissociation methods

Project description:Tissue dissociation, mechanical and/or enzymatic, is a method of disaggregating 3D connective tissue to release cells for downstream single cell analysis. Without proper controls for tissue dissociation experiments, potential artifacts can be mistaken for baseline tissue data. We hypothesized that enzymatic (collagenase/hyaluronidase) compared to mechanical dissociation leads to dissociated related artifacts not found in endogenous tumor tissue. To distinguish artifacts between enzymatic and mechanical dissociation, we compared separate enzymatic and mechanical dissociated samples with baseline samples from healthy and tumor patient whole blood, melanoma and head and neck squamous cell carcinoma (HNSCC) tumor tissues in flow cytometry, RNA sequencing and CODEX experiments. In bulk sorted tumor tissue, there is a significant difference between enzymatic and mechanical digested samples in cell stress, heat shock proteins and cell death related genes. These genes were also significantly upregulated in enzymatic over mechanical samples in the single cell RNA sequencing HNSCC tissue data. Fibroblasts and CD39+CD103+ CD8 T cells from tumor tissue, appear to require enzymatic digestion for efficient release from tissue compared to the mechanical digested samples. CD39+CD103+ CD8 tumor infiltrating lymphocytes (TILs) show different phenotypes depending on dissociation technique and tumor tissue. In tumor tissue, CD3+CD8+CD69+ T cells and gene expression were elevated in the enzymatic samples over the mechanical and baseline frozen tissue. Tissue dissociation techniques and tissue analysis from downstream applications have the potential for dissociation related artifacts that can mislead both protein and RNA sequencing data analysis in cancer research.

2023-09-19 | GSE243359 | GEO

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