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

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 t...

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Veröffentlicht in:Scientific reports Jg. 6; H. 1; S. 39296
Hauptverfasser: Iwata, Tomoaki, Kondo, Yasuteru, Kimura, Osamu, Morosawa, Tatsuki, Fujisaka, Yasuyuki, Umetsu, Teruyuki, Kogure, Takayuki, Inoue, Jun, Nakagome, Yu, Shimosegawa, Tooru
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 14.12.2016
Nature Publishing Group
Schlagworte:
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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
Online-Zugang:Volltext
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Zusammenfassung: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.
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These authors contributed equally to this work.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep39296