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:	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
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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.
AbstractList	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. 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. 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.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. 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.
ArticleNumber	39296
Author	Kogure, Takayuki Nakagome, Yu Shimosegawa, Tooru Iwata, Tomoaki Kondo, Yasuteru Kimura, Osamu Morosawa, Tatsuki Fujisaka, Yasuyuki Inoue, Jun Umetsu, Teruyuki
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Snippet	Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors....
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StartPage	39296
SubjectTerms	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
Title	PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment
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Volume	6
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