Mtp53对肿瘤免疫的调控及其在免疫治疗中的应用  

Regulation of Tumor Immunity by Mtp53 and Its Application in Immunotherapy

作　　者：曹其右 狄翠霞[2] 王俊玲[1] CAO Qi-You;DI Cui-Xia;WANG Jun-Ling(Department of Toxicology,School of Public Health,Lanzhou University,Lanzhou 730000,Gansu,China;Medical Physics Group,Biomedical Research Center,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学公共卫生学院卫生毒理学研究系,兰州730000 [2]中国科学院近代物理研究所生物医学中心医学物理室,兰州730000

出　　处：《中国生物化学与分子生物学报》2024年第8期1031-1042,共12页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金委海外及港澳学者合作研究基金项目(No.81828011);科技部国家重点研发计划(No.2018YFE0205100)资助。

摘　　要：p53是人体重要的肿瘤抑制因子,研究发现,p53在近一半的肿瘤中均发生了突变。突变p53(mtp53)发挥着促进肿瘤的作用,在肿瘤免疫中扮演着关键角色。研究证明,mtp53通过多种机制参与机体肿瘤免疫过程中的诸多环节。本文介绍了mtp53的结构和功能,并进一步探讨了mtp53对肿瘤免疫分子机制的调控,重点阐释了mtp53在促进肿瘤免疫逃逸、促进机体氧化应激、调控肿瘤相关炎症信号网络和肿瘤浸润免疫细胞募集以及分化4个方面的分子机制。最后,本文总结了mtp53对肺癌、三阴性乳腺癌和结直肠癌免疫微环境的影响,以及mtp53在癌症PD-1/PD-L1抑制剂治疗中的应用进展,以期为表达mtp53癌症的免疫治疗提供合适的方向和选择。p53 is an important tumor suppressor in the body,but research has found that p53 is one of the most frequent alterations in nearly half of human cancers.Mutant p53(mtp53)not only promotes tumor development but also serves as a pivotal factor in tumor immunity.Research has demonstrated that mtp53 participates in many aspects of tumor immune response through multiple mechanisms.We firstly describe the structure and function of mtp53,then the molecular mechanisms of mtp53 in tumor immunity,including four aspects of promoting tumor immune escape,facilitating oxidative stress,regulating tumor-associated inflammatory signaling networks and tumor-infiltrating immune cell recruitment and differentiation.Finally,we summarize the effects of mtp53 on the immune micro-environment of lung cancer,triple-negative breast cancer and colorectal cancer as well as the advances in the application of mtp53 in the treatment of cancers with PD-1/PD-L1 inhibitors,which may provide suitable directions and options for the immunotherapy of mtp53-expressing cancers.

关 键 词：P53 突变p53/mtp53 肿瘤免疫 免疫治疗 

分 类 号：Q319[生物学—遗传学]