Adipocytes promote tumor progression and induce PD-L1 expression via TNF-α/IL-6 signaling

Cancer Cell International

Jia Zhao¹  Meng-Ting Shi¹  Man-Wen Jin¹  Jing-Xia Du¹  Zhi Li¹  Hui Liu¹  Cai Zhang¹ 

[1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology;

关键词: Adipocytes;    Hepatocellular carcinoma;    Melanoma;    PD-L1;    TNF-α;    IL-6;   

DOI  :  10.1186/s12935-020-01269-w

来源: DOAJ

【 摘 要 】

Abstract Background Obesity confers increased risk for various types of cancer. PD-L1 is a key molecule in tumor immune evasion by inducing T cell exhaustion. The relationship between obesity and PD-L1 is still ambiguous. This study was designed to reveal the development of hepatocellular carcinoma and melanoma in obese mice and to investigate if adipocytes regulate PD-L1 expression and the underlying mechanism. Methods Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells and High fat diet (HFD)-induced obese mice were inoculated with B16-F1 mouse melanoma cells. Human hepatoma HepG2 cells and B16-F1 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Neutralized anti-TNF-α and anti-IL-6 antibodies and inhibitor of NF-κB or STAT3 were used to reveal the mechanism of effect of adi-CM. Results In obese mice, H22 and B16-F1 tumor tissues grew faster and PD-L1 expression in tumor tissue was increased. Adi-CM up-regulated PD-L1 level in HepG2 and B16-F1 cells in vitro. Differentiated 3T3-L1 adipocytes secreted TNF-α and IL-6, and neutralizing TNF-α and/or IL-6 reduced PD-L1 expression in adi-CM-treated cells. p-NF-κB/NF-κB level was downregulated in HepG2 and B16-F1 cells, and p-STAT3/STAT3 level was also decreased in HepG2 cells. In addition, inhibitor of NF-κB or STAT3 reversed the effect of adi-CM on PD-L1 expression. Conclusions TNF-α and IL-6 secreted by adipocytes up-regulates PD-L1 in hepatoma and B16-F1 cells, which may be at least partially involved in the role of obesity in promoting tumor progression.

【 授权许可】

Unknown