Emerging Role of the p53 Pathway in Modulating Natural Killer Cell Mediated Immunity

Abstract The p53 pathway plays an important role in role in cancer immunity. Mutation or downregulation of the proteins in the p53 pathway are prevalent in many cancers, contributing to tumor progression and immune dysregulation. Recent findings suggest that the activity of p53 within tumor cells, immune cells, and the tumor microenvironment can play an important role in modulating NK cell–mediated immunity. Consequently, efforts to restore p53 pathway activity are being actively pursued to modulate this form of immunity. This review focuses on p53 activity regulating the infiltration and activation of NK cells in the tumor immune microenvironment. Furthermore, the impact of p53 and its regulation of NK cells on immunogenic cell death within solid tumors and the abscopal effect are reviewed. Finally, future avenues for therapeutically restoring p53 activity to improve NK cell–mediated antitumor immunity and optimize the effectiveness of cancer therapies are discussed.