USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity.

ABSTRACT: The CD47/SIRPα axis conveys a 'don't eat me' signal, thereby thwarting the phagocytic clearance of tumor cells. Although blocking antibodies targeting CD47 have demonstrated promising anti-tumor effects in preclinical models, clinical trials involving human cancer patients have not yielded ideal results. Exploring the regulatory mechanisms of CD47 is imperative for devising more efficacious combinational therapies. Here, we report that inhibiting USP2 prompts CD47 degradation and reshapes the tumor microenvironment (TME), thereby enhancing anti-PD-1 immunotherapy. Mechanistically, USP2 interacts with CD47, stabilizing it through deubiquitination. USP2 inhibition destabilizes CD47, thereby boosting macrophage phagocytosis. Single-cell RNA sequencing shows USP2 inhibition reprograms TME, evi

SUBMITTER: Dai P 

PROVIDER: S-EPMC12084640 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature