Phenotype and function of CXCR5+CD45RA-CD4+ T cells were altered in HBV-related hepatocellular carcinoma and elevated serum CXCL13 predicted better prognosis.
Phenotype and function of CXCR5+CD45RA-CD4+ T cells were altered in HBV-related hepatocellular carcinoma and elevated serum CXCL13 predicted better prognosis.
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DOI：
10.18632/oncotarget.6235
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发表时间：
2015-12-29
期刊：
影响因子：
--
通讯作者：
Lu F
中科院分区：
文献类型：
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作者：
Duan Z;Gao J;Zhang L;Liang H;Huang X;Xu Q;Zhang Y;Shen T;Lu F
本研究揭示了B型肝炎病毒相关肝细胞癌（HCC）患者中循环和肿瘤浸润性T滤泡辅助细胞（Tfh），即CXCR 5 + CD 45 RA − CD 4 + T细胞及其相关细胞因子的免疫学特征。在HCC患者中，循环Tfh细胞显示CCR 7+和/或ICOS+表型，Th 2样细胞增加，Th 1样和Th 17样亚群减少。尽管HCC患者中循环Tfh细胞的总体频率没有改变，但肿瘤中浸润的CXCR 5 + CD 45 RA − CD 4 + CD 3+细胞的频率高于癌旁组织，并且Th 1样细胞是主要表型。肝癌患者外周血Tfh细胞在体外产生IL-21的能力存在缺陷，这与肿瘤组织中IL-21水平低于癌旁组织是一致的。HCC患者血清CXCL 13水平升高，与肝切除术后无复发生存率相关。这在另一个111例患者的HCC队列中得到证实，随访时间长达5年。免疫组化染色显示，低分化肿瘤中CXCR 5+或CXCL 13+细胞的百分比高于高分化肿瘤。总之，HBV相关HCC患者表现出Tfh细胞或亚群的表型改变和功能受损。CXCL 13可能是预测肝癌切除术后复发的潜在生物标志物。
The present study reveals an immunological characterization of circulating and tumor-infiltrating T follicular helper cells (Tfh), namely CXCR5+CD45RA−CD4+ T cells, and their related cytokines in hepatitis B virus-related hepatocellular carcinoma (HCC) patients. In HCC patients, circulating Tfh cells showed a CCR7+ and/or ICOS+ phenotype with increased Th2-like cells and decreased Th1-like and Th17-like subsets. Although the bulk frequency of circulating Tfh cells was not altered in HCC patients, the frequency of infiltrated CXCR5+CD45RA−CD4+ CD3+cells was higher in tumor than in para-tumor tissues, and Th1-like cells were the predominant phenotype. Circulating Tfh cells in HCC patients were defective in the production of IL-21 in vitro, which was in accordance with lower IL-21 levels in tumor tissues than in para-tumor tissues. Serum CXCL13 was increased in HCC patients and associated with recurrence-free survival after hepatectomy. This was confirmed in an additional HCC cohort of 111 patients with up to 5 years follow-up. Immunohistochemical staining indicated that the percentage of CXCR5+ or CXCL13+ cells was higher in poorly differentiated than in well-differentiated tumors. In conclusion, patients with HBV-related HCC showed altered phenotypes and impaired function of Tfh cells or subpopulations. CXCL13 could be a potential biomarker for predicting recurrence in HCC patients after hepatectomy.