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Platinum-Based TREM2 Inhibitor Suppresses Tumors by Remodeling the Immunosuppressive Microenvironment.

Tao YangShuren ZhangHao YuanYing WangLinxiang CaiHanhua ChenXiaoyu WangDongfan SongXiaohui WangZijian GuoXiaoyong Wang
Published in: Angewandte Chemie (International ed. in English) (2022)
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.
Keyphrases
  • natural killer cells
  • induced apoptosis
  • endothelial cells
  • mouse model
  • stem cells
  • anti inflammatory
  • cell cycle arrest
  • hiv infected
  • cell proliferation
  • antiretroviral therapy
  • endoplasmic reticulum stress
  • nk cells