p53是一种转录因子，调控与肿瘤抑制有关的基因的表达。p53突变介导肿瘤发生，并在人类癌症中约占50％。p53调控数百个靶基因，诱导包括凋亡、细胞周期阻滞和DNA损伤修复在内的各种细胞命运。p53还通过调节TRAIL、DR5、TLRs、Fas、PKR、ULBP1/2、CCL2、T细胞抑制配体PD-L1、促炎细胞因子、免疫细胞激活状态和抗原呈递，在抗肿瘤免疫中起重要作用。p53的遗传改变可以通过影响免疫细胞对肿瘤的招募、肿瘤微环境中的细胞因子分泌以及炎性信号通路来促进免疫逃逸。在某些情况下，p53突变会增加新抗原负荷，从而提高对免疫检查点抑制的反应。通过治疗性恢复突变的p53，可以恢复抗癌免疫细胞浸润并改善促肿瘤信号，诱导肿瘤退化。实际上，有临床证据表明，在免疫冷漠性肿瘤中，恢复p53可以诱导抗癌免疫反应。临床试验研究中，结合恢复p53的化合物或基于p53的疫苗与免疫治疗的组合，已经证明了肿瘤免疫激活和肿瘤退化，但在不同癌症类型间存在异质性。在本综述中，我们讨论了野生型和突变型p53对抗肿瘤免疫反应的影响，概述了激活p53诱导免疫反应在各种癌症类型中的临床进展，并强调了限制有效临床转化的未解开问题。版权所有 © 2023 Carlsen, Zhang, Tian, De La Cruz, George, Arnoff and El-Deiry.

p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and DNA damage repair. p53 also plays an important role in anti-tumor immunity by regulating TRAIL, DR5, TLRs, Fas, PKR, ULBP1/2, and CCL2; T-cell inhibitory ligand PD-L1; pro-inflammatory cytokines; immune cell activation state; and antigen presentation. Genetic alteration of p53 can contribute to immune evasion by influencing immune cell recruitment to the tumor, cytokine secretion in the TME, and inflammatory signaling pathways. In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Indeed, there is clinical evidence to suggest that restoring p53 can induce an anti-cancer immune response in immunologically cold tumors. Clinical trials investigating the combination of p53-restoring compounds or p53-based vaccines with immunotherapy have demonstrated anti-tumor immune activation and tumor regression with heterogeneity across cancer type. In this Review, we discuss the impact of wild-type and mutant p53 on the anti-tumor immune response, outline clinical progress as far as activating p53 to induce an immune response across a variety of cancer types, and highlight open questions limiting effective clinical translation.Copyright © 2023 Carlsen, Zhang, Tian, De La Cruz, George, Arnoff and El-Deiry.