MGAT1-Guided complex N-Glycans on CD73 regulate immune evasion in triple-negative breast cancer.

ABSTRACT: Despite the widespread application of immunotherapy, treating immune-cold tumors remains a significant challenge in cancer therapy. Using multiomic spatial analyses and experimental validation, we identify MGAT1, a glycosyltransferase, as a pivotal factor governing tumor immune response. Overexpression of MGAT1 leads to immune evasion due to aberrant elevation of CD73 membrane translocation, which suppresses CD8⁺ T cell function, especially in immune-cold triple-negative breast cancer (TNBC). Mechanistically, addition of N-acetylglucosamine to CD73 by MGAT1 enables the CD73 dimerization necessary for CD73 loading onto VAMP3, ensuring membrane fusion. We further show that THBS1 is an upstream etiological factor orchestrating the MGAT1-CD73-VAMP3-adenosine axis in suppressing CD8<

SUBMITTER: Chi JJ 

PROVIDER: S-EPMC11997035 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature