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程序性死亡配体PD-L1在肿瘤中调控机制的研究进展

Research progress on the regulatory mechanism of PD-L1 expression in tumors

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【作者】 王岳; 全纯涛; 吴红雅; 谢妮;

【Author】 WANG Yue;QUAN Chun-Tao;WU Hong-Ya;XIE Ni;Hengyang Medical School,University of South China;BioBank,Shenzhen Second People’s Hospital;Hubei 672 Integrated Traditional Chinese and Western Medicine Orthopedic Hospital;

【通讯作者】 谢妮;

【机构】 南华大学衡阳医学院; 深圳市第二人民医院生物样本库; 湖北六七二中西医结合骨科医院;

【摘要】 肿瘤新发病例逐年增长,严重影响居民身体健康并带来了沉重的医疗负担。肿瘤免疫治疗近年来异军突起,目前肿瘤免疫治疗的主要思路是通过抑制剂或对应抗体来干扰PD-1/PD-L1轴,从而解除对T细胞免疫状态的抑制,发挥杀伤肿瘤细胞的功能,因此以PD-1/PD-L1为靶点的免疫调节对抗肿瘤有重要意义。PD-L1通常在各种恶性肿瘤中表达上调,最新证据表明存在多种潜在机制或信号通路调控PD-L1表达,基于此开发特异的小分子抑制剂在抑制关键致癌信号通路的同时,还能抑制PD-L1表达,从而实现免疫检查点抑制剂联合靶向药物疗法的突破,发挥协同抗肿瘤效应。本文就癌症中PD-L1在基因突变、表观遗传修饰、转录和翻译后修饰水平的调控机制展开论述,为进一步开展联合靶向疗法提供理论基础。

【Abstract】 The incidence of cancer is increasing yearly, which seriously affects the health of residents and brings about a heavy medical burden. Tumor immunotherapy has acquired momentum in recent years. At present, the main idea of tumor immunotherapy is to interfere with the PD-1/PD-L1 axis by inhibitors or corresponding antibodies, to remove the immune-suppressed status of T cells and kill tumor cells. Therefore, it is of great significance to fight against tumors by targeting PD-1/PD-L1 for immune regulation. PD-L1 is typically high-expressed in all malignant tumors, and many potential mechanisms or signaling pathways regulate PD-L1 expression. The immune checkpoint inhibitors, combined with targeted drug therapy, can exert a synergistic anti-tumor effect based on the role of specific small molecule inhibitors to inhibit key signaling pathways and the expression of PD-L1 simultaneously.This article reviews the effects of gene mutations, epigenetic modifications, transcriptional regulation and posttranslational modification on PD-L1 in cancer, aiming to provide a theoretical basis for further development of combined targeted therapy.

【关键词】 PD-L1; PD-1; 肿瘤; 调控;
【Key words】 PD-L1; PD-1; tumors; regulation;
【基金】 国家自然科学基金项目(8217081650)
  • 【文献出处】 生命科学 ,Chinese Bulletin of Life Sciences , 编辑部邮箱 ,2023年03期
  • 【分类号】R730.2
  • 【下载频次】121
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