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Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

ABSTRACT: Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

PROVIDER: PRJNA507627 | ENA |

REPOSITORIES: ENA

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Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

Project description:Tumor immune cell compositions play a major role in response to immunotherapy but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here we identify conserved intratumoral CD4 and CD8 T cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector “transitional” into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor-reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted, are in fact a highly proliferating, clonal and dynamically differentiating cell population within the human tumor microenvironment.

2018-12-27 | GSE123139 | GEO

Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma.

Project description:Tumor immune cell compositions play a major role in response to immunotherapy, but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here, we identify conserved intratumoral CD4 and CD8 T cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector "transitional" into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted are in fact a highly proliferating, clonal, and dynamically differentiating cell population within the human tumor microenvironment.

| S-EPMC7253294 | biostudies-literature

Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

Project description:Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

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Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

Project description:Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

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Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment

Project description:Immune checkpoint blockade has shown clinical activity in a range of cancer types. To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naïve head and neck squamous cell carcinoma, we analyzed immune infiltrates in tumor biopsies from responding and non-responding patients. At baseline, a higher ratio between active (4-1BB/OX-40+) and inactive regulatory CD4+ T cells was associated with response to therapy. Furthermore, upon therapy, this active Treg population showed a profound decrease in responding patients. In an analogous process, the intratumoral dysfunctional CD8+ T cell compartment displayed a decrease in the expression of activity and dysfunction-related genes in responding patients, while in clinically non-responding patients, NK cells showed an increased cytotoxic transcriptional profile early upon treatment. These data reveal the immunological changes in response to dual PD-1 and CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive T cell compartments in responding patients, and indicate that the presence of an activated Treg compartment at baseline may be associated with response.

2023-08-07 | GSE232240 | GEO

Megadomains and superloops form dynamically during X-chromosome inactivation but are dispensable for silencing and escape

Project description:Megadomains and superloops form dynamically during X-chromosome inactivation but are dispensable for silencing and escape

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Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment

Project description:Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment

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Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

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Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

| PRJNA688690 | ENA

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

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