CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis

作者全名："Yang, Ping; Qin, Hong; Li, Yiyu; Xiao, Anhua; Zheng, Enze; Zeng, Han; Su, Chunxiao; Luo, Xiaoqing; Lu, Qiannan; Liao, Meng; Zhao, Lei; Wei, Li; Varghese, Zac; Moorhead, John F.; Chen, Yaxi; Ruan, Xiong Z."

作者地址："[Yang, Ping; Qin, Hong; Li, Yiyu; Xiao, Anhua; Zheng, Enze; Zeng, Han; Su, Chunxiao; Luo, Xiaoqing; Lu, Qiannan; Liao, Meng; Zhao, Lei; Wei, Li; Chen, Yaxi; Ruan, Xiong Z.] Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing, Peoples R China; [Yang, Ping; Qin, Hong; Li, Yiyu; Xiao, Anhua; Zheng, Enze; Zeng, Han; Su, Chunxiao; Luo, Xiaoqing; Lu, Qiannan; Liao, Meng; Zhao, Lei; Wei, Li; Chen, Yaxi; Ruan, Xiong Z.] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis,Minist Educ, Dept Infect Dis,Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China; [Varghese, Zac; Moorhead, John F.; Ruan, Xiong Z.] UCL, Univ Coll London Med Sch, Ctr Nephrol, John Moorhead Res Lab, Royal Free Campus, London, England"

通信作者："Chen, YX; Ruan, XZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing, Peoples R China.; Chen, YX; Ruan, XZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis,Minist Educ, Dept Infect Dis,Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China.; Ruan, XZ (通讯作者)，UCL, Univ Coll London Med Sch, Ctr Nephrol, John Moorhead Res Lab, Royal Free Campus, London, England."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:000864344500007

JCR分区：Q1

影响因子：16.6

年份：2022

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Liver metastasis is highly aggressive and treatment-refractory, partly due to macrophage-mediated immune suppression. Understanding the mechanisms leading to functional reprogramming of macrophages in the tumor microenvironment (TME) will benefit cancer immunotherapy. Herein, we find that the scavenger receptor CD36 is upregulated in metastasis-associated macrophages (MAMs) and deletion of CD36 in MAMs attenuates liver metastasis in mice. MAMs contain more lipid droplets and have the unique capability in engulfing tumor cell-derived long-chain fatty acids, which are carried by extracellular vesicles. The lipid-enriched vesicles are preferentially partitioned into macrophages via CD36, that fuel macrophages and trigger their tumor-promoting activities. In patients with liver metastases, high expression of CD36 correlates with protumoral M2-type MAMs infiltration, creating a highly immunosuppressive TME. Collectively, our findings uncover a mechanism by which tumor cells metabolically interact with macrophages in TME, and suggest a therapeutic potential of targeting CD36 as immunotherapy for liver metastasis."

基金机构："National Natural Science Foundation of China [32030054, 81873569]; National Key R&D Program of China [2018YFC1312700]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2020jcyj-zdxmX0007, cstc2020jcyj-msxmX0205]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [[2021]24]; 111 Project [D20028]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 32030054 to XZ.R., No. 81873569 to Y.C.); National Key R&D Program of China (No. 2018YFC1312700 to XZ.R.); the Chongqing Research Program of Basic Research and Frontier Technology (No. cstc2020jcyj-zdxmX0007 to Y.C., No. cstc2020jcyj-msxmX0205 to P.Y.); Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (No. [2021]24 to Y.C.); the 111 Project (No. D20028 to XZ.R.)."