Aberrant composition of the dendritic cell population in hepatic lymph nodes of patients with hepatocellular carcinoma

被引:26
作者
Tang, TJ
Vukosavljevic, D
Janssen, HLA
Binda, RS
Mancham, SB
Tilanus, HW
IJzermans, JNM
Drexhage, H
Kwekkeboom, J [1 ]
机构
[1] Univ Rotterdam, Ctr Med, Erasmus Med Ctr, Dept Gastroenterol & Hepatol, NL-3015 GD Rotterdam, Netherlands
[2] Univ Rotterdam, Ctr Med, Erasmus Med Ctr, Dept Surg, NL-3015 GD Rotterdam, Netherlands
[3] Univ Rotterdam, Ctr Med, Erasmus Med Ctr, Dept Immunol, NL-3015 GD Rotterdam, Netherlands
关键词
hepatocellular carcinoma; myeloid dendritic cell; plasmacytoid dendritic cell; hepatitis B virus; hepatitis C virus;
D O I
10.1016/j.humpath.2005.11.007
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:332 / 338
页数:7
相关论文
共 33 条
[1]   Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets [J].
Beckebaum, S ;
Zhang, X ;
Chen, X ;
Yu, ZY ;
Frilling, A ;
Dworacki, G ;
Grosse-Wilde, H ;
Broelsch, CE ;
Gerken, G ;
Cicinnati, VR .
CLINICAL CANCER RESEARCH, 2004, 10 (21) :7260-7269
[2]   Kinetics of the immune response during HBV and HCV infection [J].
Bertoletti, A ;
Ferrari, C .
HEPATOLOGY, 2003, 38 (01) :4-13
[3]   Immunotherapeutic strategies for hepatocellular carcinoma [J].
Butterfield, LH .
GASTROENTEROLOGY, 2004, 127 (05) :S232-S241
[4]  
Butterfield LH, 2003, CLIN CANCER RES, V9, P5902
[5]   Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent THI polarization [J].
Cella, M ;
Facchetti, F ;
Lanzavecchia, A ;
Colonna, M .
NATURE IMMUNOLOGY, 2000, 1 (04) :305-310
[6]   Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma [J].
Chau, GY ;
Wu, CW ;
Lui, WY ;
Chang, TJ ;
Kao, HL ;
Wu, LH ;
King, KL ;
Loong, CC ;
Hsia, CY ;
Chi, CW .
ANNALS OF SURGERY, 2000, 231 (04) :552-558
[7]   BDCA-2, a novel plasmacytoid dendritic cell-specific type IIC-type lectin, mediates antigen capture and is a potent inhibitor of interferon α/β induction [J].
Dzionek, A ;
Sohma, Y ;
Nagafune, J ;
Cella, M ;
Colonna, M ;
Facchetti, F ;
Günther, G ;
Johnston, I ;
Lanzavecchia, A ;
Nagasaka, T ;
Okada, T ;
Vermi, W ;
Winkels, G ;
Yamamoto, T ;
Zysk, M ;
Yamaguchi, Y ;
Schmitz, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (12) :1823-1834
[8]   Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells [J].
Gilliet, M ;
Liu, YJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (06) :695-704
[9]   Cirrhotic patients with or without hepatocellular carcinoma harbour AFP-specific T-lymphocytes that can be activated in vitro by human alpha-fetoprotein [J].
Hanke, P ;
Rabe, C ;
Serwe, M ;
Böhm, S ;
Pagenstecher, C ;
Sauerbruch, T ;
Caselmann, WH .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2002, 37 (08) :949-955
[10]  
Hartmann E, 2003, CANCER RES, V63, P6478