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 β-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 PPARα 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.
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The mass spectrometry proteomics data have been deposited to the Proteome Xchange Consortium via the PRIDE  partner repository with the dataset identifier PXD030840.
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This work was supported by the fund from the National Natural Science Foundation of China (81972749), Science and Technology Program of Liaoning Province (2018225056, 2021JH2/10300020), and Innovative Teams Project in Key Areas of Dalian (2021RT01). We are also very grateful to Professor Kuang from Sun Yat-sen University, Guangzhou, PR China for his selfless technical guidance in this experiment and Professor Yu from the Dalian Blood Center, Associate Professor Chu from Dalian Institute of Chemical Physics, Chinese Academy of Sciences for their generous help in this research. In the meanwhile, we deeply appreciate the patients’ generous support for this research.
The authors declare no competing interests.
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Liu, J., Sun, B., Guo, K. et al. Lipid-related FABP5 activation of tumor-associated monocytes fosters immune privilege via PD-L1 expression on Treg cells in hepatocellular carcinoma. Cancer Gene Ther (2022). https://doi.org/10.1038/s41417-022-00510-0