Prostaglandin E₂-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth.

ABSTRACT: Foxp3⁺ regulatory T cells (Tregs) heavily infiltrate malignant tumors and restrict antitumor immunity. These tumor-infiltrating Tregs (TI-Tregs) adopt a distinct phenotype by expressing a unique set of genes. This TI-Treg gene expression signature is conserved in TI-Tregs across species and tumor types and stages, suggesting the presence of a common inducing mechanism in the tumor microenvironment (TME). However, identity of such a mechanism remains elusive. Here, we show that prostaglandin E₂ (PGE₂) produced in TME directly acts on its receptor EP2/EP4 on Tregs to induce the TI-Treg phenotype. PGE₂ added to TCR-activated Tregs induces a set of genes, many of which are included in the TI-Treg signature, in both induced Tregs (iTregs) and naturall

SUBMITTER: Matsuura R 

PROVIDER: S-EPMC12704795 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature