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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance

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

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE237638 | GEO | 2024/02/06

REPOSITORIES: GEO

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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Mouse]

Project description:T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating T cell infiltration. Despite the identification of distinct CAF subtypes using single-cell RNA-sequencing, their specific impact on hindering T cell infiltration remains unclear, particularly in soft-tissue sarcomas (STS) characterized by low response rates to T cell-based therapies. In this study, we comprehensively characterized the STS microenvironment using murine models with distinct immune composition and scRNA-seq, leading to the identification of a unique subset of CAFs termed glycolytic cancer-associated fibroblasts (glyCAFs). GlyCAFs rely on glycolysis to impede cytotoxic T cell infiltration into the tumor parenchyma. Targeting glycolysis in glyCAFs enhances T-cell infiltration and augments the efficacy of chemotherapy. These findings highlight new avenues for combinatorial therapeutic interventions in sarcomas and other solid tumors. Further investigations and clinical trials are needed to validate these potential strategies and translate them into clinical practice.

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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Human]

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Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas.

Project description:T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating immune infiltration. Despite the identification of distinct CAF subtypes using single-cell RNA-sequencing (scRNA-seq), their functional impact on hindering T-cell infiltration remains unclear, particularly in soft-tissue sarcomas (STS) characterized by low response rates to T cell-based therapies. In this study, we characterize the STS microenvironment using murine models (in female mice) with distinct immune composition by scRNA-seq, and identify a subset of CAFs we termed glycolytic cancer-associated fibroblasts (glyCAF). GlyCAF rely on GLUT1-dependent expression of CXCL16 to impede cytotoxic T-cell infiltration into the tumor parenchyma. Targeting glycolysis decreases T-cell restrictive glyCAF accumulation at the tumor margin, thereby enhancing T-cell infiltration and augmenting the efficacy of chemotherapy. These findings highlight avenues for combinatorial therapeutic interventions in sarcomas and possibly other solid tumors. Further investigations and clinical trials are needed to validate these potential strategies and translate them into clinical practice.

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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance

Project description:Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance

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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Mouse]

Project description:Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Mouse]

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Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Human]

Project description:Cancer-associated fibroblasts metabolic targeting overcomes T-cell exclusion and chemoresistance [Human]

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Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and overcomes chemoresistance in ovarian clear cell carcinoma

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

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