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Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes (FXRPD)-P-high-L1(low) NSCLC to Anti-PD-1 Immunotherapy

文献类型：期刊论文

作者You, Wenjie1,2; Li, Lijun3,4; Sun, Deqiao3,4,5; Liu, Xueqing1; Xia, Zongjun3,4; Xue, Shan1; Chen, Bi6; Qin, Hui1; Ai, Jing3,4; Jiang, Handong1
刊名CANCER IMMUNOLOGY RESEARCH
出版日期2019-06-01
卷号7期号:6页码:990-1000
ISSN号2326-6066
DOI10.1158/2326-6066.CIR-17-0672
通讯作者Ai, Jing(jai@simm.ac.cn) ; Jiang, Handong(jianghd@163.com)
英文摘要The farnesoid X receptor (FXR) regulates inflammation and immune responses in a subset of immune-mediated diseases. We previously reported that FXR expression promotes tumor cell proliferation in non-small cell lung cancer (NSCLC). Here we study the relevance of FXR to the immune microenvironment of NSCLC. We found an inverse correlation between FXR and PD-L1 expression in a cohort of 408 NSCLC specimens; from this, we identified a subgroup of (FXRPD)-P-high-L1(low) patients. We showed that FXR downregulates PD-L1 via transrepression and other mechanisms in NSCLC. Cocultured with (FXRPD)-P-high-L1(low) NSCLC cell lines, effector function and proliferation of CD8(+) T cell in vitro are repressed. We also detected downregulation of PD-L1 in FXR-overexpressing Lewis lung carcinoma (LLC) mouse syngeneic models, indicating an (FXRPD)-P-high-L1(low) subtype in which FXR suppresses tumor-infiltrating immune cells. Anti-PD-1 therapy was effective against (FXRPD)-P-high-L1(low) mouse LLC tumors. Altogether, our findings demonstrate an immunosuppressive role for FXR in the (FXRPD)-P-high-L1(low) NSCLC subtype and provide translational insights into therapeutic response in PD-L1(low) NSCLC patients treated with anti-PD-1. We recommend (FXRPD)-P-high-L1(low) as a biomarker to predict responsiveness to anti-PD-1 immunotherapy.
WOS关键词CELL-PROLIFERATION ; IN-VITRO ; LUNG ; CANCER ; FXR ; EXPRESSION ; DOCETAXEL ; NIVOLUMAB ; ANTIBODY ; ACID
资助项目National Natural Science Foundation of China[91629104] ; National Natural Science Foundation of China[81874314] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[81773762] ; Personalized Medicines Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; Personalized Medicines Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020103]
WOS研究方向Oncology ; Immunology
语种英语
WOS记录号WOS:000470290200013
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/289717]  
专题新药研究国家重点实验室
通讯作者Ai, Jing; Jiang, Handong
作者单位1.Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Dept Resp Med, Shanghai, Peoples R China
2.Shandong Univ, Shandong Prov Hosp, Dept Resp Med, Jinan, Shandong, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Xuzhou Med Univ, Dept Resp Med, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 You, Wenjie,Li, Lijun,Sun, Deqiao,et al. Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes (FXRPD)-P-high-L1(low) NSCLC to Anti-PD-1 Immunotherapy[J]. CANCER IMMUNOLOGY RESEARCH,2019,7(6):990-1000.
APA You, Wenjie.,Li, Lijun.,Sun, Deqiao.,Liu, Xueqing.,Xia, Zongjun.,...&Jiang, Handong.(2019).Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes (FXRPD)-P-high-L1(low) NSCLC to Anti-PD-1 Immunotherapy.CANCER IMMUNOLOGY RESEARCH,7(6),990-1000.
MLA You, Wenjie,et al."Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes (FXRPD)-P-high-L1(low) NSCLC to Anti-PD-1 Immunotherapy".CANCER IMMUNOLOGY RESEARCH 7.6(2019):990-1000.

入库方式： OAI收割

来源：上海药物研究所

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