Amphiregulin couples IL1RL1⁺ regulatory T cells and cancer-associated fibroblasts to impede antitumor immunity.

ABSTRACT: Regulatory T (T_reg) cells and cancer-associated fibroblasts (CAFs) jointly promote tumor immune tolerance and tumorigenesis. The molecular apparatus that drives T_reg cell and CAF coordination in the tumor microenvironment (TME) remains elusive. Interleukin 33 (IL-33) has been shown to enhance fibrosis and IL1RL1⁺ T_reg cell accumulation during tumorigenesis and tissue repair. We demonstrated that IL1RL1 signaling in T_reg cells greatly dampened the antitumor activity of both IL-33 and PD-1 blockade. Whole tumor single-cell RNA sequencing (scRNA-seq) analysis and blockade experiments revealed that the amphiregulin (AREG)-epidermal growth factor receptor (EGFR) axis mediated cross-talk between IL1RL1⁺ T_reg cells and C

SUBMITTER: Sun R 

PROVIDER: S-EPMC10446484 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature