Mutation in p53 is the most frequent event in cancer development and a leading cause of cancer therapy resistance due to evasion of the apoptosis cascade. Beyond chemotherapies and radiation therapies, growing evidence indicates that p53-mutant tumors are resistant to a broad range of immune-based therapies, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T, and hematopoietic stem cell transplantation (HSCT). This highlights the role of p53 mutations in driving immune evasion of tumor cells. In this review, we first summarize recent studies revealing mechanisms by which p53-mutant tumors evade immune surveillance from T cells, natural killer (NK) cells, and macrophages. We then review how these mutant tumor cells reshape the tumor microenvironment (TME), modulating bystander cells such as macrophages, neutrophils, and regulatory T (Treg) cells to foster immunosuppression. Additionally, we review clinical observations indicative of immune evasion associated with p53 loss or mutations. Finally, we discuss therapeutic strategies to enhance immune response in p53 wild-type (WT) or mutant tumors.
p53基因突变是癌症发生中最常见的事件，也是导致癌症治疗抵抗的主要原因之一，因其能够逃避凋亡级联反应。除化疗和放疗外，越来越多的证据表明，p53突变肿瘤对多种免疫疗法具有抵抗性，如免疫检查点抑制剂、嵌合抗原受体（CAR）T细胞疗法以及造血干细胞移植（HSCT）。这突显了p53突变在驱动肿瘤细胞免疫逃逸中的关键作用。本文首先综述了近期研究，揭示p53突变肿瘤如何逃避T细胞、自然杀伤（NK）细胞和巨噬细胞的免疫监视机制。随后，我们探讨了这些突变肿瘤细胞如何重塑肿瘤微环境（TME），通过调节巨噬细胞、中性粒细胞和调节性T（Treg）细胞等旁观者细胞来促进免疫抑制。此外，本文还回顾了与p53缺失或突变相关的免疫逃逸临床观察证据。最后，我们讨论了增强p53野生型（WT）或突变肿瘤免疫应答的治疗策略。
TP53Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications
肿瘤(癌症)患者之家