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

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

doi:10.1016/j.humpath.2005.11.007

« Previous Next »Human Pathology
Volume 37, Issue 3 , Pages 332-338, March 2006

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

Thjon J. Tang, MD, PhD
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Dragica Vukosavljevic, MSc
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Harry L.A. Janssen, MD, PhD
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Rekha S. Binda, MSc
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Shanta Mancham, MSc
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Hugo W. Tilanus, MD, PhD
- Department of Surgery, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Jan N.M. IJzermans, MD, PhD
- Department of Surgery, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Hemmo Drexhage, PhD
- Department of Immunology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Jaap Kwekkeboom, PhD
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
- Corresponding author.

Received 8 September 2005; received in revised form 8 November 2005; accepted 9 November 2005. published online 27 January 2006.

Summary

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.

Keywords: Hepatocellular carcinoma, Myeloid dendritic cell, Plasmacytoid dendritic cell, Hepatitis B virus, Hepatitis C virus