Reprogramming CD8+ T-cell Branched N-Glycosylation Limits Exhaustion, Enhancing Cytotoxicity and Tumor Killing.

ABSTRACT: T-cell therapies have transformed cancer treatment. Although surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell-mediated tumor immunity remains an area of active investigation. In this study, we show that the intratumoral T-cell glycome is altered early in human colorectal cancer, with substantial changes in branched N-glycans. We demonstrated that CD8+ T cells expressing β1,6-GlcNAc-branched N-glycans adopted an exhausted phenotype, marked by increased PD1 and Tim3 expression. CRISPR-Cas9 deletion of key branching glycosyltransferase genes revealed that Mgat5 played a prominent role in T-cell exhaustion. In culture-based assays and tumor studies, Mgat5 deletion in CD8+ T cells resulted in impr

SUBMITTER: Azevedo CM 

PROVIDER: S-EPMC12489179 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature