微泡
糖酵解
转移
表型
细胞生物学
肿瘤微环境
癌症研究
巨噬细胞
生物
微泡
重编程
免疫学
癌症
细胞
小RNA
新陈代谢
体外
基因
肿瘤细胞
内分泌学
生物化学
遗传学
作者
Samantha M. Morrissey,Fan Zhang,Chuan‐Fan Ding,Diego E. Montoya-Durango,Xiaoling Hu,Chenghui Yang,Zhen Wang,Yuan Fang,Matthew P. Fox,Huang‐Ge Zhang,Haixun Guo,David Tieri,Maiying Kong,Corey T. Watson,Robert A. Mitchell,Xiang Zhang,Kelly M. McMasters,Jian Huang,Jun Yan
出处
期刊:Cell Metabolism
[Elsevier]
日期:2021-10-01
卷期号:33 (10): 2040-2058.e10
被引量:207
标识
DOI:10.1016/j.cmet.2021.09.002
摘要
One of the defining characteristics of a pre-metastatic niche, a fundamental requirement for primary tumor metastasis, is infiltration of immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDEs) polarize macrophages toward an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent, glycolytic-dominant metabolic reprogramming. TDE signaling through TLR2 and NF-κB leads to increased glucose uptake. TDEs also stimulate elevated NOS2, which inhibits mitochondrial oxidative phosphorylation resulting in increased conversion of pyruvate to lactate. Lactate feeds back on NF-κB, further increasing PD-L1. Analysis of metastasis-negative lymph nodes of non-small-cell lung cancer patients revealed that macrophage PD-L1 positively correlates with levels of GLUT-1 and vesicle release gene YKT6 from primary tumors. Collectively, our study provides a novel mechanism by which macrophages within a pre-metastatic niche acquire their immunosuppressive phenotype and identifies an important link among exosomes, metabolism, and metastasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI