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

Tomoaki Iwata, Yasuteru Kondo, Osamu Kimura, Tatsuki Morosawa, Yasuyuki Fujisaka, Teruyuki Umetsu, Takayuki Kogure, Jun Inoue, Yu Nakagome, Tooru Shimosegawa

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40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number39296
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Dec 14

ASJC Scopus subject areas

  • General

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