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Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells

ABSTRACT: Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells

PROVIDER: PRJNA513067 | ENA |

REPOSITORIES: ENA

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Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4<sup>+</sup> T Cells.

Project description: Not available

| S-EPMC6934378 | biostudies-literature

Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells

Project description:We used single-cell mRNA sequencing to analyze the response of tumor-specific CD4+ tumor infiltrating lymphocytes (TILs) and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identified TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy.

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Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human

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A Subset of Genes Can Distinguish between Bortezomib Responsive Versus Bortezomib Resistant Myeloma

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scRNA-seq of allo-reactive CD4+ T cells

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Interactions between reactive oxygen species stress and brassinosteroid hormone signaling in Arabidopsis seedlings

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DNA accessibility in reactive and non-reactive CMV specific CD8+ lymphocytes

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Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19

Project description:The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present a large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T helper (TH)1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.

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