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

doi:10.1158/2326-6066.CIR-17-0672

	Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes (FXRPD)-P-high-L1(low) NSCLC to Anti-PD-1 Immunotherapy
	You, Wenjie 1,2; Li, Lijun 3,4; Sun, Deqiao3,4,5 ; Liu, Xueqing 1; Xia, Zongjun 3,4; Xue, Shan 1; Chen, Bi 6; Qin, Hui 1; Ai, Jing 3,4; Jiang, Handong 1
	2019-06
发表期刊	CANCER IMMUNOLOGY RESEARCH
ISSN	2326-6066
卷号	7 期号:6 页码:990-1000
发表状态	已发表
DOI	10.1158/2326-6066.CIR-17-0672
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	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
WOS类目	Oncology ; Immunology
WOS记录号	WOS:000470290200013
出版者	AMER ASSOC CANCER RESEARCH
WOS关键词	CELL-PROLIFERATION ; IN-VITRO ; LUNG ; CANCER ; FXR ; EXPRESSION ; DOCETAXEL ; NIVOLUMAB ; ANTIBODY ; ACID
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/48999
专题	生命科学与技术学院_硕士生
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.