期刊
CANCER GENE THERAPY
卷 29, 期 12, 页码 1951-1960出版社
SPRINGERNATURE
DOI: 10.1038/s41417-022-00510-0
关键词
-
类别
资金
- National Natural Science Foundation of China [81972749]
- Science and Technology Program of Liaoning Province [2018225056, 2021JH2/10300020]
- Innovative Teams Project in Key Areas of Dalian [2021RT01]
The accumulation of FABP5 in monocytes/macrophages in the tumor microenvironment promotes immune tolerance formation through metabolic reprogramming and IL-10 expression. Furthermore, elevated FABP5 levels are negatively associated with the overall survival time of hepatocellular carcinoma patients.
Monocytes/macrophages, a plastic and heterogeneous cell population of the tumor microenvironment (TME), can constitute a major component of most solid tumors. Under the pressure of rapid proliferation of the tumor, monocytes/macrophages can be educated and foster immune tolerance via metabolic reprogramming. Our studies have shown that the activation of FABP5, a lipid-binding protein, decreases the rate of beta-oxidation causing the accumulation of lipid droplets in monocytes. We found that hepatocellular carcinoma cells (HCC) increased IL-10 secretion by monocytes, which depended on the expression of FABP5 and suppressing of the PPAR alpha pathway. Moreover, the elevated level of IL-10 promotes PD-L1 expression on Treg cells via the JNK-STAT3 pathway activation. We also observed that elevation of FABP5 in monocytes was negatively related to HCC patients' overall survival time. Thus, FABP5 promotes monocyte/macrophage lipid accumulation, fosters immune tolerance formation, and might represent itself as a therapeutic target in both tumor-associated monocytes (TAMs) and cancer cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据