title: PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment.
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.
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.|Department of Hepatology, Sendai Kousei Hospital, 4-15 Hirose, Aoba, Sendai City, 980-0873, Miyagi, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Morosawa
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujisaka
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Umetsu
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kogure
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakagome
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai City, 980-8574, Miyagi, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis*; D001773:Blood Cells / Q000737:chemistry / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000737:chemistry / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human