Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Huang H

PROVIDER: S-EPMC9197998 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Huang Huocong H Wang Zhaoning Z Zhang Yuqing Y Pradhan Rachana N RN Ganguly Debolina D Chandra Raghav R Murimwa Gilbert G Wright Steven S Gu Xiaowu X Maddipati Ravikanth R Müller Sören S Turley Shannon J SJ Brekken Rolf A RA

Cancer cell 20220505 6

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 apCAF ...[more]

PMID: 35523176

Similar Datasets

Project description:Biomaterials allow for the precision control over the combination and release of cargo needed to engineer cell outcomes. These capabilities are particularly attractive as new candidate therapies to treat autoimmune diseases, conditions where dysfunctional immune cells create pathogenic tissue environments during attack of self-molecules termed self-antigens. Here we extend past studies showing combinations of a small molecule immunomodulator co-delivered with self-antigen induces antigen-specific regulatory T cells. In particular, we sought to elucidate how different ratios of these components loaded in degradable polymer particles shape the antigen presenting cell (APC) -T cell interactions that drive differentiation of T cells toward either inflammatory or regulatory phenotypes. Using rapamycin (rapa) as a modulatory cue and myelin self-peptide (myelin oligodendrocyte glycoprotein- MOG) - self-antigen attacked during multiple sclerosis (MS), we integrate these components into polymer particles over a range of ratios and concentrations without altering the physicochemical properties of the particles. Using primary cell co-cultures, we show that while all ratios of rapa:MOG significantly decreased expression of co-stimulation molecules on dendritic cells (DCs), these levels were insensitive to the specific ratio. During co-culture with primary T cell receptor transgenic T cells, we demonstrate that the ratio of rapa:MOG controls the expansion and differentiation of these cells. In particular, at shorter time points, higher ratios induce regulatory T cells most efficiently, while at longer time points the processes are not sensitive to the specific ratio. We also found corresponding changes in gene expression and inflammatory cytokine secretion during these times. The in vitro results in this study contribute to in vitro regulatory T cell expansion techniques, as well as provide insight into future studies to explore other modulatory effects of rapa such as induction of maintenance or survival cues.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets