Resumen
Immune checkpoint blockade with anti-PD-1 antibodies blocks the development of oral squamous cell carcinomas (OSCCs) in preclinical models. Understanding whether the genetic alterations that accumulate during oral cancer development affect the response to PD-1 inhibitors is critical to identify patients who may benefit from immunoprevention interventions. Using genetically engineered mouse models that develop carcinogen-induced oral tumors that differ on the mutational status of the p53 gene, we demonstrated that expression of gain-of-function mutant p53 in the epithelial cells of the oral lesions promotes resistance to the immunopreventive effects of anti-PD-1. These novel findings could guide patient-specific strategies for oral cancer immunoprevention based on p53 profiling.