CBX6 induces CD8⁺ T cell exhaustion and tumor development in esophageal squamous cell carcinoma through SMARCD1-mediated CCL8 secretion and lactate efflux.

ABSTRACT: This study investigates the functions of chromobox 6 (CBX6) in esophageal squamous cell carcinoma (ESCC) and delves into its functional mechanisms. The bioinformatics insights suggested that CBX6 was overexpressed in ESCC and linked to dismal prognosis. Cbx6 knockdown was induced in mouse mEC25 cells. This procedure curbed the proliferation and migration of mEC25 cells and reduced exhaustion of the co-cultured CD8⁺ T cells. In vivo, Cbx6 knockdown in mEC25 cells reduced tumorigenesis while enhancing immune activity in mice. Further experiments showed that CBX6 reduced CD8⁺ T cell cytotoxicity by secreting C-C motif chemokine ligand 8 (CCL8) and promoting monocarboxylate transporter 4 (MCT4)-mediated lactate transport. Regarding the mechanism, CBX6 regulated the expres

SUBMITTER: Wang L 

PROVIDER: S-EPMC12616757 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature