Radiofrequency ablation for the treatment of HCC – Maybe much more than simple tumor destruction?

COMMENTARY ON Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Gastroenterology, 2010 May;138(5):1931–1942. Eup 2010 Jan 11. Copyright 2010. Abstract reprinted with permission from Elsevier Inc. www.ncbi.nlm.gov/pubmed/20060829 Abstract: Background & Aims Radiofrequency thermal ablation (RFA) is a minimally invasive technique used as standard local therapy of hepatocellular carcinoma and second-line treatment for metastatic liver tumors. Studies in preclinical models and in patients have shown that thermal destruction of tumor tissue can enhance anti-tumor cellular responses, but our knowledge of its impact on natural killer (NK) cells is still very limited. Methods Thirty-seven patients undergoing RFA for hepatocellular carcinoma were studied for peripheral blood lymphocytes counts followed by phenotypic and functional characterization of NK-cell population. Results Peripheral blood lymphocytes kinetics revealed an increased frequency and absolute number of NK-cells expressing higher levels of activatory along with reduced levels of inhibitory NK receptors, and increased functional NK-cell activity. A prevalent expansion of the CD3(−)CD56(dim) NK subset was observed compared to the CD3(−)CD56(bright) counterpart. Interferon-gamma production, anti-K562 cell-cytotoxicity, and antibody-dependent cell-cytotoxicity, appeared consistently increased in terms of both absolute activity and killing efficiency at 4weeks after RFA, as compared to baseline. Interestingly, when recurrence-free survival was assessed in two groups of patients separated according to higher vs lower enhancement of cytotoxicity and/or interferon-gamma production, a significant difference was observed, thus suggesting a potential predictive role of NK functional assays on efficacy of RFA. Conclusions RFA can lead to stimulation of NK-cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. This observation may be relevant for development of adjuvant immunotherapeutic strategies aimed at enhancing NK-cell responses against primary and metastatic liver tumors.