biostudies-literatureLai XNational High-Level Talents Special Support Program Youth PanelGeneral Projects sponsored by Natural Science Foundation of ShanghaiNational Natural Science Foundation of ChinaOutstanding Youth Fund of Guangdong ProvinceNational Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai General Hospitale20625https://www.ebi.ac.uk/biostudies/studies/S-EPMC12915102biostudies-literatureUnknown13(10)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 spoAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Targeting DAP5 Disrupts Alternate Mode of Translational Initiation in Tregs and Potentiates Antitumor Immunity.PMC12915102822037518207266225ZR1401302NRCTM(SH)-2025-05824021002022B151502010902.06.01.23.16932070918Yang HHuang CZhang JFeng XFeng YBao WLin ZWang JLai XPan GLi YZhao SXie CfalseTargeting DAP5 Disrupts Alternate Mode of Translational Initiation in Tregs and Potentiates Antitumor Immunity.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 spo2026-01-01T00:00:00Z2026 Feb2026-07-16T05:35:56.824Z2026-07-09T10:39:22.804ZS-EPMC129151024145745910.1002/advs.202520625