title: Increase in CD14+HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis.
abstract: Myeloid-derived suppressor cells (MDSCs) are known as key immune regulators in various human malignancies, and it is reported that CD14(+)HLA-DR(-/low) MDSCs are increased in hepatocellular carcinoma (HCC) patients. However, the host factors that regulate the frequency and the effect on the prognosis of HCC patients are still unclear. We investigated these issues and clarified the relationships between a feature of MDSCs and host factors in HCC patients. We examined the frequency of MDSCs in 123 HCC patients, 30 chronic liver disease patients without HCC, and 13 healthy controls by flow cytometric analysis. The relationships between the clinical features and the frequency of MDSCs were analyzed. In 33 patients who received curative radiofrequency ablation (RFA) therapy, we examined the impact of MDSCs on HCC recurrence. The frequency of MDSCs in HCC patients was significantly increased. It was correlated with tumor progression, but not with the degree of liver fibrosis and inflammation. In terms of serum cytokines, the concentrations of IL-10, IL-13, and vascular endothelial growth factor were significantly correlated with the frequency of MDSCs. In HCC patients who received curative RFA therapy, the frequency of MDSCs after treatment showed various changes and was inversely correlated with recurrence-free survival time. The frequency of MDSCs is correlated with tumor progression, and this frequency after RFA is inversely correlated with the prognosis of HCC patients. Patients with a high frequency of MDSCs after RFA should be closely followed and the inhibition of MDSCs may improve the prognosis of patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan. bnkyo78@gmail.com
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Arihara
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitahara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takata
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Arai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D017115:Catheter Ablation; D002452:Cell Count; D016207:Cytokines / Q000097:blood / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000706:statistics & numerical data; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D018793:Interleukin-13 / Q000097:blood / Q000276:immunology; D053208:Kaplan-Meier Estimate; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D008297:Male; D015999:Multivariate Analysis; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000276:immunology
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10