Tang Thjon J, Vukosavljevic Dragica, Janssen Harry L A, Binda Rekha S, Mancham Shanta, Tilanus Hugo W, Ijzermans Jan N M, Drexhage Hemmo, Kwekkeboom Jaap
Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Hum Pathol. 2006 Mar;37(3):332-8. doi: 10.1016/j.humpath.2005.11.007.
Patients with hepatocellular carcinoma (HCC) are characterized by a weak T-cell response to their tumor, and chronic carriers of hepatitis B virus or hepatitis C virus have a poor T-cell response against the virus. These inadequate T-cell responses may be due to insufficient activation of the T cells by dendritic cells (DCs). Because lymph nodes (LNs) are the primary site of antigen-specific T-cell activation, we hypothesized that hepatic LNs of patients with HCC and/or chronic viral hepatitis might have aberrant compositions of their DC populations. To address this hypothesis, we enumerated mature myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in hepatic LNs by quantitative immunohistochemistry. Patients with HCC and chronic viral hepatitis and patients with chronic viral hepatitis without HCC were compared with patients with liver inflammation of nonviral etiology and with organ donors with healthy livers. The numbers of PDCs and mature MDCs in hepatic LNs of patients with chronic viral hepatitis did not differ from those of patients with liver inflammation of nonviral etiology nor from individuals with healthy livers. However, hepatic LNs of patients with HBV or HCV infection complicated by HCC showed a 1.5-fold reduction in numbers of mature MDCs and a 4-fold increase in numbers of PDCs in their T-cell areas compared with those of patients with viral hepatitis only (P <.01). In conclusion, patients with HCC have an aberrant composition of the DC population in their hepatic LNs. This may be one of the causes of the inadequate T-cell response against HCC in these patients.
肝细胞癌(HCC)患者的特征是对其肿瘤的T细胞反应较弱,而乙型肝炎病毒或丙型肝炎病毒的慢性携带者对病毒的T细胞反应较差。这些T细胞反应不足可能是由于树突状细胞(DC)对T细胞的激活不足所致。由于淋巴结(LN)是抗原特异性T细胞激活的主要部位,我们推测HCC和/或慢性病毒性肝炎患者的肝LN可能具有异常的DC群体组成。为了验证这一假设,我们通过定量免疫组织化学方法对肝LN中的成熟髓样DC(MDC)和浆细胞样DC(PDC)进行了计数。将HCC和慢性病毒性肝炎患者、无HCC的慢性病毒性肝炎患者与非病毒性病因引起的肝脏炎症患者以及肝脏健康的器官供体进行了比较。慢性病毒性肝炎患者肝LN中的PDC和成熟MDC数量与非病毒性病因引起的肝脏炎症患者以及肝脏健康的个体相比没有差异。然而,与仅患有病毒性肝炎的患者相比,合并HCC的HBV或HCV感染患者的肝LN在其T细胞区域的成熟MDC数量减少了1.5倍,PDC数量增加了4倍(P <.01)。总之,HCC患者肝LN中的DC群体组成异常。这可能是这些患者对HCC的T细胞反应不足的原因之一。