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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (2)

ABSTRACT: Here we report transcriptional and TCR specificities associated with melanoma patient TIL populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203183 | GEO | 2022/05/20

REPOSITORIES: GEO

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (1)

Project description:Here we report transcriptional specificities associated with murine Trp1 CD4+ and Trp1 CD4+CD8+ T cells isolated from B16 melanoma tumor resections.

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (3)

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (5)

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions.

Project description:Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics.

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Here we report ATAC sequencing data from sorted antigen specific Trp1 CD4+ and CD4+CD8+, and Pmel CD8+ and CD8+CD4+ T cells in steady state (naïve, no tumor) mice and also in B16-tumor bearing animals

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