Activation of dendritic cells by local ablation of hepatocellular carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
HCC ablation induced a functional transient activation of MDC but not of PDC associated with increased serum levels of TNF-alpha and IL-1beta.


CONCLUSIONS
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.
Ali
Mona Y
MY
Department of Medicine II, ,University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
Grimm
Christian F
CF
Ritter
Marcus
M
Mohr
Leonhard
L
Allgaier
Hans-Peter
HP
Weth
Robert
R
Bocher
Wulf O
WO
Endrulat
Katja
K
Blum
Hubert E
HE
Geissler
Michael
M
D039521:CD11c Antigen / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D017115:Catheter Ablation; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D007375:Interleukin-1 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053650:Interleukin-3 Receptor alpha Subunit; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039521:CD11c Antigen; C115022:IL3RA protein, human; D007375:Interleukin-1; D053650:Interleukin-3 Receptor alpha Subunit; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12