PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

• Published in: Scientific reports Vol. 6; no. 1; p. 39296
• Main Authors: Iwata, Tomoaki, Kondo, Yasuteru, Kimura, Osamu, Morosawa, Tatsuki, Fujisaka, Yasuyuki, Umetsu, Teruyuki, Kogure, Takayuki, Inoue, Jun, Nakagome, Yu, Shimosegawa, Tooru
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.12.2016; Nature Publishing Group
• Subjects: 13; 13/106; 13/21; 13/31; 692/4020/4021; 692/4020/4021/1607; Aged; Arsenic; B7-H1 Antigen - analysis; Blood Cells - chemistry; Blood Cells - immunology; Carcinoma, Hepatocellular - pathology; Cell Count; Cells, Cultured; Coculture Techniques; Color; Female; Flow Cytometry; Hepatocellular carcinoma; Hepatocytes; Humanities and Social Sciences; Humans; Immunoregulation; Japan; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - immunology; Liver cancer; Liver Neoplasms - pathology; Macrophage colony-stimulating factor; Male; Middle Aged; multidisciplinary; Myeloid-Derived Suppressor Cells - chemistry; Myeloid-Derived Suppressor Cells - immunology; PD-L1 protein; Peripheral blood; Science; Suppressor cells; Tumor cell lines; Tumor Microenvironment; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep39296

Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1 + MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1 + MDSCs in comparison to those from healthy subjects ( p  < 0.001). The percentages of PD-L1 + MDSCs were reduced by curative treatment for HCC ( p  < 0.05), and the percentages of PD-L1 + MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1 + MDSCs were significantly increased compared with control ( p  < 0.05). The expression of M-CSF and VEGFA was higher in the cell lines that strongly induced PD-L1 + MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1 + MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1 + MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1 + MDSCs as a new biomarker of HCC.