1. TP53 Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications.
- Author
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Wang, Chuqi, Tan, Jordan Yong Ming, Chitkara, Nishtha, and Bhatt, Shruti
- Subjects
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HEMATOPOIETIC stem cell transplantation , *KILLER cells , *MACROPHAGES , *APOPTOSIS , *CELL physiology , *NEUTROPHILS , *IMMUNOTHERAPY , *IMMUNE checkpoint inhibitors , *ONCOGENES , *GENETIC mutation , *TUMORS , *IMMUNOSUPPRESSION ,TUMOR genetics - Abstract
Simple Summary: p53 mutations are prevalent across a variety of human cancers and are regarded as a major obstacle in cancer therapy. These mutations can confer resistance to apoptosis and cell cycle arrest, contributing to multidrug resistance in tumors. Recent studies have uncovered important immunomodulatory functions of p53, but these functions are still underappreciated compared to its other well-known roles. This review aims to summarize the latest literature on immune evasion in p53-mutant tumors and explore the potential of targeting p53 to enhance anti-tumor immunity. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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