STAT蛋白
贾纳斯激酶
流式细胞术
单克隆抗体
车站3
斯达
JAK-STAT信号通路
信号转导
激活剂(遗传学)
化学
PD-L1
癌症研究
细胞生物学
生物化学
生物
抗体
免疫疗法
分子生物学
免疫系统
免疫学
受体
酪氨酸激酶
作者
Xiaobo Wang,Wenlong Xu,Zeng-Yiyi Wang,Qian Yu,Yuan Li,Yihang Liu,Jiayan Sang,Wei Li,Sanyong Zhu,Wei Jiang,Zengxia Li,Wen Zhang,Yongjun Dang
标识
DOI:10.1021/acs.jnatprod.3c00811
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-γ-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.
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