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Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer

ABSTRACT: Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer

PROVIDER: PRJNA807147 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18033727_1.fastq.gz	Fastqsanger.gz
	SRR18033727_2.fastq.gz	Fastqsanger.gz
	SRR18033728_1.fastq.gz	Fastqsanger.gz
	SRR18033728_2.fastq.gz	Fastqsanger.gz
	SRR18033729_1.fastq.gz	Fastqsanger.gz

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Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer

Project description:Recent studies have identified a unique cancer-associated fibroblast (CAF) population called antigen-presenting CAFs (apCAFs). apCAFs are characterized by the expression of MHC II molecules, suggesting a function in regulating tumor immunity. Here by integrating multiple single cell RNA sequencing studies and performing robust lineage tracing assays, we found that apCAFs are derived from mesothelial cells. During pancreatic cancer progression, mesothelial cells form apCAFs by down-regulating mesothelial features and gaining fibroblastic features, a process induced by IL-1 and TGFβ. apCAFs directly ligate and induce naïve CD4+ T cells into regulatory T cells (Tregs) in an antigen-specific manner. Moreover, targeting the mesothelial cell marker mesothelin by a monoclonal antibody can effectively inhibit mesothelial cell to apCAF transition and the Treg formation induced by apCAFs. Taken together, our study elucidates an important but neglected cell type that regulates tumor immunity and may lead to targeted therapies that can overcome immune evasion in cancer.

2022-02-18 | GSE196740 | GEO

Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer.

Project description:Recent studies have identified a unique cancer-associated fibroblast (CAF) population termed antigen-presenting CAFs (apCAFs), characterized by the expression of major histocompatibility complex class II molecules, suggesting a function in regulating tumor immunity. Here, by integrating multiple single-cell RNA-sequencing studies and performing robust lineage-tracing assays, we find that apCAFs are derived from mesothelial cells. During pancreatic cancer progression, mesothelial cells form apCAFs by downregulating mesothelial features and gaining fibroblastic features, a process induced by interleukin-1 and transforming growth factor β. apCAFs directly ligate and induce naive CD4+ T cells into regulatory T cells (Tregs) in an antigen-specific manner. Moreover, treatment with an antibody targeting the mesothelial cell marker mesothelin can effectively inhibit mesothelial cell to apCAF transition and Treg formation induced by apCAFs. Taken together, our study elucidates how mesothelial cells may contribute to immune evasion in pancreatic cancer and provides insight on strategies to enhance cancer immune therapy.

| S-EPMC9197998 | biostudies-literature

Cancer-Associated Mesothelial Cell-Derived ANGPTL4 and STC1 Promote the early steps of Ovarian Cancer metastasis

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2024-04-05 | E-MTAB-13698 | biostudies-arrayexpress

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