Murine double minute 2(MDM2)plays an essential role in the cell cycle,apoptosis,DNA repair,and oncogene activation through p53-dependent and p53-independent signaling pathways.Several preclinical studies have shown th...Murine double minute 2(MDM2)plays an essential role in the cell cycle,apoptosis,DNA repair,and oncogene activation through p53-dependent and p53-independent signaling pathways.Several preclinical studies have shown that MDM2 is involved in tumor immune evasion.Therefore,MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention.In recent years,im-mune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic.Howev-er,the effectiveness of a single agent is only approximately 20%-40%,which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins.Here,we reviewed the role of MDM2 in regulating the immune microenvironment,tumor immune evasion,and hyperprogression during immunotherapy.In addition,we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tu-mors with MDM2 overexpression or amplification.The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China (No.82202869,82260491,82160459)Jiangxi Province"Double Thousand Program" (China) (No.jxsq 2023201108)+1 种基金China Postdoctoral Science Foundation (No.338937)the Jiangxi Provincial Natural Science Foundation (China) (No.20232ACB206044).
文摘Murine double minute 2(MDM2)plays an essential role in the cell cycle,apoptosis,DNA repair,and oncogene activation through p53-dependent and p53-independent signaling pathways.Several preclinical studies have shown that MDM2 is involved in tumor immune evasion.Therefore,MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention.In recent years,im-mune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic.Howev-er,the effectiveness of a single agent is only approximately 20%-40%,which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins.Here,we reviewed the role of MDM2 in regulating the immune microenvironment,tumor immune evasion,and hyperprogression during immunotherapy.In addition,we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tu-mors with MDM2 overexpression or amplification.The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.
