ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4⁺ macrophage infiltration.

ABSTRACT: Enoblituzumab, an immunotherapeutic agent targeting CD276, shows both safety and efficacy in activating T cells and oligodendrocyte-like cells against various cancers. Preclinical studies and mouse models suggest that therapies targeting CD276 may outperform PD1/PD-L1 blockade. However, data from mouse models indicate a significant non-responsive population to anti-CD276 treatment, with the mechanisms of resistance still unclear. In this study, we evaluate the activity of anti-CD276 antibodies in a chemically-induced murine model of head and neck squamous cell carcinoma. Using models of induced and orthotopic carcinogenesis, we identify ITGB6 as a key gene mediating differential responses to anti-CD276 treatment. Through single-cell RNA sequencing and gene-knockout mouse models, we find th

SUBMITTER: Zhang C 

PROVIDER: S-EPMC11329676 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature