MYC and p53 Alterations Cooperate through VEGF Signaling to Repress Cytotoxic T-cell and Immunotherapy Responses in Prostate Cancer.

ABSTRACT: Patients with castration-resistant prostate cancer (CRPC) are generally unresponsive to tumor-targeted treatments and immunotherapies. Genetic alterations acquired during the evolution of CRPC may affect antitumor immunity and immunotherapy responses, which could inform personalized therapeutic strategies. Using our innovative electroporation-based mouse models, we generated distinct genetic subtypes of CRPC found in patients and uncovered unique immune microenvironments. Specifically, mouse and human prostate tumors with MYC amplification and p53 disruption had weak cytotoxic lymphocyte infiltration and an overall dismal prognosis. MYC and p53 cooperated to induce tumor-intrinsic secretion of VEGF, which signaled through VEGFR2 expressed on CD8+ T cells to directly inhibit T-cell migratio

SUBMITTER: Murphy KC 

PROVIDER: S-EPMC12471896 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature