CD36
清道夫受体
转移
肿瘤微环境
癌症研究
免疫系统
免疫疗法
串扰
重编程
癌症免疫疗法
生物
化学
细胞生物学
癌症
免疫学
细胞
受体
胆固醇
生物化学
脂蛋白
物理
光学
遗传学
作者
Ping Yang,Hong Qin,Yiyu Li,Anhua Xiao,Enze Zheng,Han Zeng,Chunxiao Su,Xiaofang Luo,Qi Lu,Meng Liao,Lei Zhao,Li Wei,Zac Varghese,John F. Moorhead,Yaxi Chen,Xiong Z. Ruan
标识
DOI:10.1038/s41467-022-33349-y
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.
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