Sokotrasterol Sulfate Suppresses IFN-γ-Induced PD-L1 Expression by Inhibiting JAK Activity

作者全名："Wang, Xiaobo; Xu, Wenlong; Wang, Zengyiyi; Yu, Qian; Yuan, Li; Liu, Yihang; Sang, Jinpeng; Li, Wei; Zhu, Sanyong; Jiang, Wei; Li, Zengxia; Zhang, Wen; Dang, Yongjun"

作者地址："[Wang, Xiaobo; Xu, Wenlong; Yu, Qian; Jiang, Wei; Li, Zengxia] Fudan Univ, Sch Basic Med Sci, Key Lab Metab & Mol Med, Minist Educ,Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China; [Wang, Zengyiyi; Zhang, Wen] Tongji Univ, Sch Med, Shanghai 200092, Peoples R China; [Yuan, Li; Zhang, Wen] Naval Med Univ, Sch Pharm, Shanghai 200433, Peoples R China; [Liu, Yihang; Zhu, Sanyong; Dang, Yongjun] Chongqing Med Univ, Affiliated Hosp 2, Basic Med Res & Innovat Ctr Novel Target & Therape, Inst Life Sci,Coll Pharm, Chongqing 400010, Peoples R China; [Sang, Jinpeng; Li, Wei] China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Nanjing 211198, Peoples R China; [Zhu, Sanyong] Ocean Univ China, Key Lab Marine Drugs, Minist Educ, Qingdao 266003, Peoples R China; [Zhu, Sanyong] Ocean Univ China, Sch Med & Pharm, Shandong Prov Key Lab Glycosci & Glycotechnol, Qingdao 266003, Peoples R China"

通信作者："Jiang, W; Li, ZX (通讯作者)，Fudan Univ, Sch Basic Med Sci, Key Lab Metab & Mol Med, Minist Educ,Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China.; Zhang, W (通讯作者)，Tongji Univ, Sch Med, Shanghai 200092, Peoples R China.; Zhang, W (通讯作者)，Naval Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.; Zhu, SY; Dang, YJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Basic Med Res & Innovat Ctr Novel Target & Therape, Inst Life Sci,Coll Pharm, Chongqing 400010, Peoples R China.; Zhu, SY (通讯作者)，Ocean Univ China, Key Lab Marine Drugs, Minist Educ, Qingdao 266003, Peoples R China.; Zhu, SY (通讯作者)，Ocean Univ China, Sch Med & Pharm, Shandong Prov Key Lab Glycosci & Glycotechnol, Qingdao 266003, Peoples R China."

来源：JOURNAL OF NATURAL PRODUCTS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001176240200001

JCR分区：Q1

影响因子：5.1

年份：2024

卷号：　

期号：　

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结束页：　

文献类型：Article; Early Access

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摘要："PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-gamma-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent."

基金机构："National Natural Science Foundation of China [81820108030, 22137002, 21877016, 92253305, 82273021, 81972621]; National Natural Science Foundation of China [2022YFC2804800]; National Key Research and Development Program of China; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning; Open Research Fund Program of Key Laboratory of Marine Drugs, Ministry of Education (Ocean University of China) [CXQT21016]; University Innovation Research Group in Chongqing [CQYC20200302119]; Chongqing Talent Program Project; High-Level Innovation Platform Cultivation Plan of Chongqing; Natural Science Innovation and Development Foundation of Chongqing"

基金资助正文："This work was supported by the National Natural Science Foundation of China (no. 81820108030 to W.Z., 22137002, 21877016 to Y.D., and 92253305, 82273021, 81972621 to W.J.), the National Key Research and Development Program of China (No. 2022YFC2804800), Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (to W.J.), Open Research Fund Program of Key Laboratory of Marine Drugs, Ministry of Education (Ocean University of China) (to S.Z.), University Innovation Research Group in Chongqing (No. CXQT21016 to Y.D.), Chongqing Talent Program Project (No. CQYC20200302119 to Y.D.), High-Level Innovation Platform Cultivation Plan of Chongqing (to Y.D.), and Joint Fund of the Natural Science Innovation and Development Foundation of Chongqing (to Y.D.)."