Chen Yu-Chi, Bazewicz Christopher G, Dinavahi Saketh S, Huntington Nicholas D, Schell Todd D, Robertson Gavin P
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
The Melanoma and Skin Cancer Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Mol Cancer Ther. 2025 Apr 2;24(4):523-535. doi: 10.1158/1535-7163.MCT-24-0325.
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.
p53信号通路在癌症免疫中发挥着重要作用。p53信号通路中的蛋白质发生突变或下调在许多癌症中普遍存在,这有助于肿瘤进展和免疫失调。最近的研究结果表明,p53在肿瘤细胞、免疫细胞和肿瘤微环境中的活性在调节自然杀伤(NK)细胞介导的免疫中可发挥重要作用。因此,人们正在积极努力恢复p53信号通路的活性,以调节这种免疫形式。本综述聚焦于p53活性对肿瘤免疫微环境中NK细胞浸润和激活的调节。此外,还综述了p53及其对NK细胞的调节对实体瘤内免疫原性细胞死亡和远隔效应的影响。最后,讨论了通过治疗性恢复p53活性来改善NK细胞介导的抗肿瘤免疫和优化癌症治疗效果的未来途径。