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肝癌患者中 CD14+HLA-DR-/low 髓源抑制细胞的增加及其对预后的影响。

Increase in CD14+HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis.

机构信息

Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

出版信息

Cancer Immunol Immunother. 2013 Aug;62(8):1421-30. doi: 10.1007/s00262-013-1447-1. Epub 2013 Jun 14.

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.

摘要

髓系来源的抑制细胞(MDSCs)是各种人类恶性肿瘤中关键的免疫调节剂,据报道 CD14(+)HLA-DR(-/low) MDSCs 在肝癌(HCC)患者中增加。然而,调节 HCC 患者频率和对预后影响的宿主因素仍不清楚。我们研究了这些问题,并阐明了 MDSCs 的特征与 HCC 患者宿主因素之间的关系。我们通过流式细胞术分析检查了 123 例 HCC 患者、30 例无 HCC 的慢性肝病患者和 13 名健康对照者中 MDSCs 的频率。分析了 MDSCs 频率与临床特征之间的关系。在接受根治性射频消融(RFA)治疗的 33 例患者中,我们检查了 MDSCs 对 HCC 复发的影响。HCC 患者中 MDSCs 的频率明显增加。它与肿瘤进展相关,但与肝纤维化和炎症程度无关。就血清细胞因子而言,IL-10、IL-13 和血管内皮生长因子的浓度与 MDSCs 的频率显著相关。在接受根治性 RFA 治疗的 HCC 患者中,治疗后 MDSCs 的频率发生了各种变化,与无复发生存时间呈负相关。MDSCs 的频率与肿瘤进展相关,而 RFA 后的这种频率与 HCC 患者的预后呈负相关。RFA 后 MDSCs 频率较高的患者应密切随访,抑制 MDSCs 可能改善患者的预后。

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