肿瘤微环境
癌症研究
化学
细胞毒性
细胞毒性T细胞
奥沙利铂
体内
体外
癌症
结直肠癌
生物
生物化学
肿瘤细胞
遗传学
生物技术
作者
Tao Yang,Shuren Zhang,Hao Yuan,Ying Wang,Linxiang Cai,Hanhua Chen,Xiaoyu Wang,Dongfan Song,Xiaohui Wang,Zijian Guo,Xiaoyong Wang
标识
DOI:10.1002/anie.202213337
摘要
Abstract Triggering receptor expressed on myeloid cells‐2 (TREM2) is a key pro‐tumorigenic marker of tumor‐infiltrating macrophages, showing potent immunosuppressive activity in tumor microenvironment. A platinum(IV) complex OPA derived from oxaliplatin (OP) and artesunate (ART) exhibited direct cytotoxicity against human colon cancer cells and immunomodulatory activity to inhibit TREM2 on macrophages in vitro and vivo. Furthermore, OPA deterred the tumor growth in mouse models bearing MC38 colorectal tumor by reducing the number of CD206 + and CX 3 CR1 + immunosuppressive macrophages; it also promoted the expansion and infiltration of immunostimulatory dendritic, cytotoxic T, and natural killer cells. OPA is the first small‐molecular TREM2 inhibitor capable of relieving immunosuppressive tumor microenvironment and enhancing chemical anticancer efficiency of a platinum drug, thus showing typical characteristics of a chemoimmunotherapeutic agent.
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