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Regulatory T cells converted from T helper 1 cells in tumors suppress cancer immunity via CD39

ABSTRACT: Although Foxp3-expressing regulatory T (Treg) cells are widely believed to impede anti-tumor immunity, their regulation and functional mechanisms are not well understood. Here, through characterization of multiple cancer models, we identified substantial periphery-induced Treg cells in the tumor microenvironment, depletion of which provoked anti-tumor responses and conferred potent therapeutic effects by increasing CD8+ T cell numbers and cytolytic function. Through fate-mapping and transfer experiments, we found IFN-γ-expressing T helper (Th) 1 cells developed into Treg cells in tumors, in response to TGF-β signaling. Hence, tumor-resident Treg cells highly expressed T-bet, which was essential for their development and function. CD39, highly expressed by T-bet+ Treg cells in both mouse and human tumors, is required for Treg suppression of CD8+ T cell response. In summary, our study has elucidated a developmental pathway of intra-tumoral Treg cells and implicated new ways of targeting them in cancer patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE240961 | GEO | 2024/02/26

REPOSITORIES: GEO

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