TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization

作     者：Lifang Zhao Hongyan Zhang Xueqing Liu Shan Xue Dongfang Chen Jing Zou Handong Jiang Lifang Zhao;Hongyan Zhang;Xueqing Liu;Shan Xue;Dongfang Chen;Jing Zou;Handong Jiang

作者机构：Department of Respiratory and Critical Care MedicineRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第2期

页      面：787-800页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81874314 and 81903633) “Yangfan”project of Shanghai Science and Technology Commission(19YF1428700,China) 

主　　题：TGR5 Bile acids Tumor-associated macrophages(TAMs) Tumor microenvironment(TME) Non-small cell lung cancer(NSCLC) Antitumor immunity Immunotherapy c AMP-STAT3/STAT6 

摘      要：The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages,and plays a critical role in regulating inflammatory *** previous work has shown its role in promoting the progression of non-small cell lung cancer(NSCLC),yet the mechanism remains ***,using Tgr5-knockout mice,we show that TGR5 is required for M2 polarization of tumorassociated macrophages(TAMs)and suppresses antitumor immunity in NSCLC via involving TAMsmediated CD8+T cell ***,we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating c AMP-STAT3/STAT6 *** of c AMP production restores M2-like phenotypes in TGR5-deficient *** NSCLC tissues from human patients,the expression of TGR5 is associated with the infiltration of *** co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC ***,this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC,highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.