TY - JOUR
T1 - Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages
AU - Su, Pan
AU - Wang, Qiang
AU - Bi, Enguang
AU - Ma, Xingzhe
AU - Liu, Lintao
AU - Yang, Maojie
AU - Qian, Jianfei
AU - Yi, Qing
N1 - Funding Information:
This work was supported in part by NIH/NCI R01s CA200539, CA211073, CA214811, and CA239255 grants and by Cancer Prevention & Research Institute of Texas Recruitment of Established Investigator Award (RR180044). We thank Research Core Services in Lerner Research Institute, Cleveland Clinic and Houston Methodist Research Institute for their support. We especially thank Tidyomics for their technical support for single-cell sequencing data analysis.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Tumor-associated macrophages (TAM) are important tumor-promoting cells. However, the mechanisms underlying how the tumor and its microenvironment reprogram these cells remain elusive. Here we report that lipids play a crucial role in generating TAMs in the tumor microenvironment (TME). Macrophages from both human and murine tumor tissues were enriched with lipids due to increased lipid uptake by macrophages. TAMs expressed elevated levels of the scavenger receptor CD36, accumulated lipids, and used fatty acid oxidation (FAO) instead of glycolysis for energy. High levels of FAO promoted mitochondrial oxidative phosphorylation, production of reactive oxygen species, phosphorylation of JAK1, and dephosphorylation of SHP1, leading to STAT6 activation and transcription of genes that regulate TAM generation and function. These processes were critical for TAM polarization and activity, both in vitro and in vivo. In summary, we highlight the importance of lipid metabolism in the differentiation and function of protumor TAMs in the TME.
AB - Tumor-associated macrophages (TAM) are important tumor-promoting cells. However, the mechanisms underlying how the tumor and its microenvironment reprogram these cells remain elusive. Here we report that lipids play a crucial role in generating TAMs in the tumor microenvironment (TME). Macrophages from both human and murine tumor tissues were enriched with lipids due to increased lipid uptake by macrophages. TAMs expressed elevated levels of the scavenger receptor CD36, accumulated lipids, and used fatty acid oxidation (FAO) instead of glycolysis for energy. High levels of FAO promoted mitochondrial oxidative phosphorylation, production of reactive oxygen species, phosphorylation of JAK1, and dephosphorylation of SHP1, leading to STAT6 activation and transcription of genes that regulate TAM generation and function. These processes were critical for TAM polarization and activity, both in vitro and in vivo. In summary, we highlight the importance of lipid metabolism in the differentiation and function of protumor TAMs in the TME.
UR - http://www.scopus.com/inward/record.url?scp=85082824374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082824374&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-19-2994
DO - 10.1158/0008-5472.CAN-19-2994
M3 - Article
C2 - 32015091
AN - SCOPUS:85082824374
VL - 80
SP - 1438
EP - 1450
JO - Cancer research
JF - Cancer research
SN - 0008-5472
IS - 7
ER -