Targeting DAP5 Disrupts Alternate Mode of Translational Initiation in Tregs and Potentiates Antitumor Immunity.

ABSTRACT: Regulatory T cells (Tregs) can thrive in the harsh tumor microenvironment (TME) to dampen antitumor immunity. Chronic stresses within TME compromise canonical cap-dependent translation (CDT), which compromises effector T cell function but not Treg persistence. Death-associated protein 5 (DAP5/eIF4G2), a non-classical translational scaffold, has been reported to support human Treg differentiation in vitro, but its functions in thymic Treg development, peripheral Treg homeostasis, and tumor-infiltrating Treg (ti-Treg) fitness remain unclear. Here, it is shown that DAP5 expression positively correlates with ti-Treg frequencies in both colorectal cancer patients and murine subcutaneous tumors. Mice with homozygous Dap5 deletion in Tregs has intact thymic and peripheral Treg development but spo

SUBMITTER: Lai X 

PROVIDER: S-EPMC12915102 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature