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ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells

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

ORGANISM(S): Mus musculus

PROVIDER: GSE288967 | GEO | 2025/07/07

REPOSITORIES: GEO

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ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [RNA-seq]

Project description:During persistent antigen stimulation, PD-1+CD8 T cells are maintained by progenitor exhausted PD-1+TCF-1+CD8 T cells (Tpex). Tpex respond to PD-1 blockade, and regulation of Tpex differentiation into more functional Tex is of major interest for cancer immunotherapies. Tpex express high levels of Inducible Costimulator (ICOS), but the role of ICOS for PD-1+CD8 T cell responses has not been addressed. In chronic infection, ICOS-deficiency increased both number and quality of virus-specific CD8 T cells, with accumulation of effector-like Tex due to enhanced survival. Mechanistically, loss of ICOS signaling potentiated FoxO1 activity and memory features of Tpex. In mice with established chronic infection, ICOS-Ligand blockade resulted in expansion of effector-like Tex and reduction in viral load. In a mouse model of hepatocellular carcinoma, ICOS inhibition improved cytokine production by tumor-specific PD-1+CD8 T cells and delayed tumor growth. Overall, we show that ICOS constrains CD8 T cell responses during chronic antigen exposure.

2025-07-07 | GSE270420 | GEO

ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [ATAC-seq]

Project description:During persistent antigen stimulation, PD-1+CD8 T cells are maintained by progenitor exhausted PD-1+TCF-1+CD8 T cells (Tpex). Tpex respond to PD-1 blockade, and regulation of Tpex differentiation into more functional Tex is of major interest for cancer immunotherapies. Tpex express high levels of Inducible Costimulator (ICOS), but the role of ICOS for PD-1+CD8 T cell responses has not been addressed. In chronic infection, ICOS-deficiency increased both number and quality of virus-specific CD8 T cells, with accumulation of effector-like Tex due to enhanced survival. Mechanistically, loss of ICOS signaling potentiated FoxO1 activity and memory features of Tpex. ICOS-deficient Tex displayed enhanced survival and improved cytokine production. In chronically-infected mice, ICOS-Ligand blockade expanded effector-like Tex, reduced viral load and potentiated anti-PD-L1 therapy. In a mouse model of hepatocellular carcinoma, ICOS inhibition improved cytokine production by tumor-specific PD-1+CD8 T cells and sensitized tumors to PD-1 targeted therapy. Overall, we show that sustained ICOS costimulation limits CD8 T cell responses during chronic antigen exposure.

2025-07-07 | GSE288889 | GEO

ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells

Project description:ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells

| PRJNA1220123 | ENA

ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [RNA-seq]

Project description:ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [RNA-seq]

| PRJNA1126605 | ENA

ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [ATAC-seq]

Project description:ICOS limits memory-like properties and function of exhausted PD-1+ CD8 T cells [ATAC-seq]

| PRJNA1219685 | ENA

Deletion of a state-specific PD-1 enhancer modulates exhausted T cell fate and function

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

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A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells

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Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells

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

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Gene expression profiles of CD8+ partial memory T cells (Tpm) compared to naive, effector and memory CD8+ T cells

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

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Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.

Project description: Not available

| S-EPMC5484795 | biostudies-literature

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