Cancer ATF4-mediated CD58 endocytosis impairs anti-tumor immunity and immunotherapy.

ABSTRACT: Co-stimulatory molecules are imperative for CD8⁺ T cells to eliminate target cell and maintain sustained cytotoxicity. Despite an advanced understanding of the co-stimulatory molecules deficiency that results in tumor escape, the tumor cell-intrinsic mechanisms that regulate co-stimulatory molecules remain enigmatic, and an in-depth dissection could facilitate the improvement of treatment options. To this end, in this study, we report that the deficiency of the critical costimulatory molecule CD58, mediated by the expression of ATF4 in tumor cells, impairs the formation of immunological synapses (IS) and leads to the deterioration of antitumor immune function of CD8⁺ T cells. Mechanistically, ATF4 transcriptionally upregulated dynamin 1 (DNM1) expression leading to DN

SUBMITTER: Zeng H 

PROVIDER: S-EPMC11863482 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature