Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
J Med Virol. 2019 Jul;91(7):1319-1328. doi: 10.1002/jmv.25428. Epub 2019 Feb 25.
Myeloid-derived suppressor cells (MDSCs) play a pivotal role in tumor immunity and induction of immune tolerance to a variety of antitumor effectors, including T lymphocytes. Herein, we tried to evaluate the frequency and clinical significance of MDSCs and different lymphocyte subsets in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).
Four groups were enrolled; chronic HCV (CHC; n = 40), HCV-related liver cirrhosis (n = 40), HCV-related HCC (HCV-HCC; n = 75), and healthy control group (n = 20). The percentage of peripheral lymphocytes subsets and total MDSCs with their main two subsets; monocytic (M-MDSCs) and granulocytic (G-MDSCs) was evaluated by flow cytometry.
The frequency of total MSDCs and M-MDSCs was significantly elevated in HCV-HCC especially patients with advanced stage HCC compared with those with early-stage HCC. The frequency of total MSDCs and M-MDSCs was positively correlated with ALT, AFP, and HCV viral load and negatively correlated with CD8 T-cell frequency. CD4 T cells were significantly decreased in HCV-HCC patients. The frequency of CD4 T cells and CD8 T cells was negatively correlated with AFP and AST, but not with albumin or HCV viral load.
Taken together, our data suggest that MDSCs, M-MDSCs, and lymphocyte subsets are associated with the development and progression of HCV-related HCC.
髓源性抑制细胞(MDSC)在肿瘤免疫中发挥关键作用,并诱导对多种抗肿瘤效应物(包括 T 淋巴细胞)的免疫耐受。在此,我们尝试评估丙型肝炎病毒(HCV)相关肝细胞癌(HCC)患者中 MDSC 及不同淋巴细胞亚群的频率及其临床意义。
共纳入 4 组人群;慢性 HCV(CHC;n = 40)、HCV 相关肝硬化(n = 40)、HCV 相关 HCC(HCV-HCC;n = 75)和健康对照组(n = 20)。采用流式细胞术评估外周血淋巴细胞亚群和总 MDSC 及其主要两个亚群(单核细胞来源 MDSC,M-MDSC 和粒细胞来源 MDSC,G-MDSC)的比例。
与早期 HCC 患者相比,HCV-HCC 尤其是晚期 HCC 患者中总 MDSC 和 M-MDSC 的频率明显升高。总 MDSC 和 M-MDSC 的频率与 ALT、AFP 和 HCV 病毒载量呈正相关,与 CD8 T 细胞频率呈负相关。HCV-HCC 患者 CD4 T 细胞明显减少。CD4 和 CD8 T 细胞的频率与 AFP 和 AST 呈负相关,但与白蛋白或 HCV 病毒载量无关。
综上所述,我们的数据表明 MDSC、M-MDSC 和淋巴细胞亚群与 HCV 相关 HCC 的发生和发展有关。