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CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE198423 | GEO | 2022/03/14

REPOSITORIES: GEO

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CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas.

Project description:Tumor-infiltrating CD8 + T cells progressively lose functionality and fail to reject tumors. The underlying mechanism and re-programing induced by checkpoint blockers are incompletely understood. We show here that genetic ablation or pharmacological inhibition of histone lysine methyltransferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1. In the absence of Suv39h1, anti-PD-1 induces alternative activation pathways allowing survival and differentiation of IFNγ and Granzyme B producing effector cells that express negative checkpoint molecules, but do not reach final exhaustion. Their transcriptional program correlates with that of melanoma patients responding to immune-checkpoint blockade and identifies the emergence of cytolytic-effector tumor-infiltrating lymphocytes as a biomarker of clinical response. Anti-PD-1 favors chromatin opening in loci linked to T-cell activation, memory and pluripotency, but in the absence of Suv39h1, cells acquire accessibility in cytolytic effector loci. Overall, Suv39h1 inhibition enhances anti-tumor immune responses, alone or combined with anti-PD-1, suggesting that Suv39h1 is an "epigenetic checkpoint" for tumor immunity.

| S-EPMC9243005 | biostudies-literature

CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [scRNA-seq]

Project description:Purpose: We show that genetic ablation or pharmacological inhibition of H3K9-methyl transferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1.

2022-03-14 | GSE198422 | GEO

CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [ATAC-seq]

Project description:Purpose: We show that genetic ablation or pharmacological inhibition of H3K9-methyl transferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1.

2022-03-14 | GSE198421 | GEO

CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas

Project description:CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas

| PRJNA815051 | ENA

CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [scRNA-seq]

Project description:CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [scRNA-seq]

| PRJNA815054 | ENA

CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [ATAC-seq]

Project description:CD8+ T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas [ATAC-seq]

| PRJNA815055 | ENA

Anti-BRAF mutation drug resistance enhances EGFR expression in melanomas

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-17 | E-GEOD-45649 | biostudies-arrayexpress

Disease-specific exhaustion features and PD-1 immunotherapy responsiveness of antigen-specific CD8+ T cells at single-cell resolution

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

2022-11-29 | GSE152628 | GEO

IL-6 signaling in CD8 T cells promotes resistance to anti-PD-L1 immunotherapy

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

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ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome

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