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

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-specific 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 flow 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 significantly 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 benefit from a prolonged increase in cytolytic activity. The immune-modulatory effects of RFA need further investigations in multimodality anticancer therapies.

Keywords

Liver cancer / radiofrequency ablation / immune response / interferon gamma / peripheral blood mononuclear cells

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