Activation of dendritic cells by local ablation of hepatocellular carcinoma

• Published in: Journal of hepatology Vol. 43; no. 5; pp. 817 - 822
• Main Authors: Ali, Mona Y., Grimm, Christian F., Ritter, Marcus, Mohr, Leonhard, Allgaier, Hans-Peter, Weth, Robert, Bocher, Wulf O., Endrulat, Katja, Blum, Hubert E., Geissler, Michael
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01-11-2005; Elsevier
• Subjects: Biological and medical sciences; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Catheter Ablation; CD11c Antigen - metabolism; Cell Separation; CTL; Cytokines; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Human; Humans; Immunotherapy; Interleukin-1 - blood; Interleukin-12 - blood; Interleukin-3 Receptor alpha Subunit; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lymphocyte Activation; Medical sciences; Neoplasm Metastasis; Neoplasm Recurrence, Local - prevention & control; Receptors, Interleukin-3 - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tolerance; Tumor Necrosis Factor-alpha - metabolism; Tumors; Human; Dendritic cells; Cytokines; Tolerance; HCC; CTL; AFP; MDC; PDC; Dendritic cell; Digestive diseases; Hepatic disease; Hepatocellular carcinoma; Activation; Malignant tumor
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.04.016

Local ablation methods are an effective treatment for hepatocellular carcinoma (HCC). The rate of recurrence or development of intra-hepatic metastases may be lowered by antitumoral immune responses. Since HCCs are in general only weakly immunogenic, cell injury induced by local tumor ablation (PEI/RFTA) may increase HCC immunogenicity and may release endogenous adjuvants that activate dendritic cells (DC). The aim of the study, therefore, was the analysis whether PEI or RFTA induced injury results in an adjuvant effect for immune responses to HCCs.
Eight HCC patients were treated with PEI or RFTA and serially analyzed for 4 weeks. Plasmocytoid (PDC) and myeloid dendritic cells (MDC) were analyzed directly ex vivo and in vitro using FACS and proliferation assays.
HCC ablation induced a functional transient activation of MDC but not of PDC associated with increased serum levels of TNF-α and IL-1β.
These findings suggest that the combination of PEI or RFTA and active antigen specific immunotherapeutic approaches using DCs is a promising approach for the induction of sustained antitumoral immune responses aiming at the reduction of tumor recurrence and metastases in HCC patients.