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Original Article

Long-term immune-modulatory side effects of radiofrequency
Long-term immune-modulatory side effects of radiofrequency
ablation in patients with liver metastases and hepatocellular
ablation in patients with liver metastases and hepatocellular
carcinoma
carcinoma

1
1
Thaddeus Till Wissniowski , Thomas Gress , Pietro Di Fazio 2
1 Division of Gastroenterology, Philipps University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
2 Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Baldingerstrasse, 35043 Marburg, Germany

ABSTRACT
Aim: Used as a palliative therapy for unresectable liver cancer, radiofrequency ablation (RFA) is associated with the induction
of immunological responses. Here, we show strong evidence of tumor-specifi c peripheral blood mononuclear cells (PBMCs)
12 months after RFA. Methods: Three patients with colorectal cancer (CRC) metastases to the liver and two patients with
primary hepatocellular carcinoma (HCC) were enrolled in this study. PBMC, isolated 12 months after RFA, were stimulated
with normal and tumor tissue lysate. Interferon gamma secretion was evaluated by fl ow cytometry and indirectly, by luciferase
assay for adenylate kinase activity in PBMC-stimulated lysates of target cells. Baseline data were detected before RFA and
4 weeks after treatment. Results: Two CRC patients and one HCC patient had recurrence-free survival. One patient with CRC
developed secondary metastases; one patient with HCC developed a local recurrence. Recurrence-free patients showed a
signifi cantly higher cytolytic activity of PBMC against matched tumor cells 12 months after RFA treatment. Interestingly, patients
with malignant recurrence showed a decreased cytolytic activity. Conclusion: RFA seems to overcome immune-tolerance
toward tumor antigens and/or presents new tumor antigens. Patients seem to benefi t from a prolonged increase in cytolytic
activity. The immune-modulatory effects of RFA need further investigations in multimodality anticancer therapies.

Key words: Liver cancer; radiofrequency ablation; immune response; interferon gamma; peripheral blood mononuclear cells

Address for correspondence:
Address for correspondence:
Dr. Pietro Di Fazio, Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Baldingerstrasse, 35041 Marburg,
Germany. E-mail: difazio@med.uni-marburg.de
Received: 12-02-2015, Accepted: 20-05-2015

INTRODUCTION can achieve, in selected patients, a survival prolongation time
comparable to surgical resection.
Surgical resection is still the gold standard for the treatment
of hepatocellular carcinoma (HCC) and liver metastases of An earlier study suggested that RFA has adjunctive
colorectal cancer (CRC). However, more than 75% of these immune-modulatory side effects. By using the VX 2
[5]
patients are elected as unresectable due to the volume and hepatoma model in rabbits, we showed that RFA can
localization of the tumor. Radiofrequency ablation (RFA) is a induce a strong mononuclear infiltration around the
common therapy option for unresectable liver tumors. [1-4] It implanted tumor. More recently, we demonstrated
was shown that RFA and laser-induced thermotherapy (LiTT) a marked tumor-specific peripheral T cell response
in RFA-treated vs. untreated rabbits with the VX 2
Access this article online hepatoma. [6,7] We further investigated whether this strong
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Website: immune response to RFA can be observed in humans.
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http://www.hrjournal.net/ We observed that significantly elevated levels of CD8 T
cells appeared 4 weeks after RFA, and this effect lasted at
least up to 8 weeks after RFA. There was also significant
DOI:
10.4103/2394-5079.158024 cytolytic activity of isolated peripheral blood mononuclear
cells (PBMCs) 8 weeks after RFA. [8]

92 Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015