SHP2作为抗肿瘤治疗靶点的价值及其在肿瘤免疫治疗中的应用  

The value of SHP2 as an anti-tumor therapeutic target and its application in tumor immunotherapy

作　　者：张玥 汪越(综述)[1,2] 魏嘉(审校) ZHANG Yue;WANG Yue;WEI Jia(The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China;Clinical Cancer Institute of Nanjing University)

机构地区：[1]南京大学医学院附属鼓楼医院肿瘤中心,南京210008 [2]南京大学临床肿瘤学研究所

出　　处：《实用肿瘤学杂志》2022年第6期513-519,共7页Practical Oncology Journal

基　　金：江苏省杰出青年基金资助项目(编号:BK20190001);中央高校基本科研业务费专项资金资助(编号:0214-14380506)。

摘　　要：包含Src同源2结构域的蛋白酪氨酸磷酸酶2(Src homology region 2-containing protein tyrosine phosphatase 2,SHP2)是目前唯一被证实具有促癌作用的细胞质蛋白酪氨酸磷酸酶,在多种恶性肿瘤中高表达。SHP2可以通过介导受体酪氨酸激酶(Receptor tyrosine kinase, RTK)下游的RAS/ERK、PI3K/Akt和JAK/STAT等信号通路促进肿瘤发生发展,影响肿瘤预后。同时,SHP2参与调控PD-1/PD-L1、CTLA-4、BLTA和TIGIT等免疫检查点信号通路,对于肿瘤微环境中各种免疫细胞都有重要的调节作用。靶向SHP2不仅可以通过抑制RTK下游信号通路,还可以通过改善免疫微环境治疗恶性肿瘤。因此,SHP2具有免疫与靶向双重治疗肿瘤的功能,作为抗肿瘤治疗的靶点展现出极高的潜能与价值。Src homology region 2-containing protein tyrosine phosphatase 2(SHP2)is the only cytoplasmic protein tyrosine phosphatase that has been confirmed to promote cancer.There are highly expressed in a variety of malignant tumors.SHP2 can promote tumor development and affect tumor prognosis by mediating RAS/ERK,PI3 K/Akt, JAK/STAT and other signal pathways downstream of receptor tyrosine kinase(RTK).At the same time, SHP2 is involved in the regulation of immune checkpoint signaling pathways such as PD-1/PD-L1,CTLA-4,BLTA and TIGIT,and plays an important role in regulating various immune cells in the tumor microenvironment.Targeting SHP2 can treat malignant tumors not only by inhibiting RTK downstream signaling pathways, but also by improving the immune microenvironment.Therefore, SHP2 has the function of dual treatment tumor by immunity and targeting, and it shows extremely high potential and value as a target for anti-tumor therapy.

关 键 词：包含Src同源2结构域的蛋白酪氨酸磷酸酶2 肿瘤 肿瘤免疫微环境 免疫治疗 

分 类 号：R73[医药卫生—肿瘤]