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

IF 5.3 2区医学 Q1 ONCOLOGY Molecular Cancer Therapeutics Pub Date : 2024-10-29 DOI:10.1158/1535-7163.MCT-24-0325

Yu-Chi Chen, Christopher G Bazewicz, Saketh S Dinavahi, Nicholas D Huntington, Todd D Schell, Gavin P Robertson

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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 modulating natural killer (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 the activation of NK cells in the tumor immune microenvironment, which are illustrated in the Graphical Abstract for this review. Furthermore, impact of p53 and its regulation of NK cells on immunogenic cell death within solid tumors and the abscopal effect is reviewed. Finally, future avenues for therapeutically restoring p53 activity to improve NK cell-mediated anti-tumor immunity and optimize the effectiveness of cancer therapies are discussed.

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p53 通路在调节自然杀伤细胞介导的免疫中的新作用。

p53 通路在癌症免疫中发挥着重要作用。在许多癌症中，p53 通路中的蛋白质普遍发生突变或下调，导致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对自然杀伤细胞（NK）介导的免疫起着重要的调节作用。因此，人们正在积极努力恢复 p53 通路的活性，以调节这种形式的免疫。本综述的重点是 p53 活性调节 NK 细胞在肿瘤免疫微环境中的浸润和活化。此外，还综述了 p53 及其对 NK 细胞的调控对实体瘤内免疫原性细胞死亡和脱落效应的影响。最后，还讨论了恢复 p53 活性以改善 NK 细胞介导的抗肿瘤免疫力和优化癌症疗法有效性的未来治疗途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer Therapeutics 医学-肿瘤学

CiteScore

11.20

自引率

1.80%

发文量

331

审稿时长

3 months

期刊介绍： Molecular Cancer Therapeutics will focus on basic research that has implications for cancer therapeutics in the following areas: Experimental Cancer Therapeutics, Identification of Molecular Targets, Targets for Chemoprevention, New Models, Cancer Chemistry and Drug Discovery, Molecular and Cellular Pharmacology, Molecular Classification of Tumors, and Bioinformatics and Computational Molecular Biology. The journal provides a publication forum for these emerging disciplines that is focused specifically on cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.