Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses

Alessandro Zerbini, Massimo Pilli, Amalia Penna, Guido Pelosi, Claudia Schianchi, Atim Molinari, Simona Schivazappa, Carlo Zibera, Francesco F. Fagnoni, Carlo Ferrari, Gabriele Missale

Research output: Contribution to journalArticle

Abstract

Radiofrequency thermal ablation (RFA) destroys tumoral tissue generating a local necrosis followed by marked inflammatory response with a dense T-cell infiltrate. In this study, we tested whether hepatocellular carcinoma thermal ablation can induce or enhance T-cell responses specific for hepatocellular carcinoma-associated antigens. Peripheral blood mononuclear cells derived from 20 patients with hepatocellular carcinoma were stimulated before and a month after RFA treatment with autologous hepatocellular carcinoma-derived protein lysates obtained before and immediately after RFA treatment. The effect of thermal ablation on memory T-cell responses to recall antigens [tetanus toxoid, protein purified derivative (PPD), Escherichia coli] was also assessed. T-cell reactivity was analyzed in an IFN-γ enzyme-linked immunospot assay and by intracellular IFN-γ staining. Treatment was followed by a significant increase of patients responsive either to tumor antigens derived from both the untreated hepatocellular carcinoma tissue (P <0.05) and the necrotic tumor (P <0.01) and by a higher frequency of circulating tumor-specific T cells. T-cell responses to recall antigens were also significantly augmented. Phenotypic analysis of circulating T and natural killer cells showed an increased expression of activation and cytotoxic surface markers. However, tumor-specific T-cell responses were not associated with protection from hepatocellular carcinoma relapse. Evidence of tumor immune escape was provided in one patient by the evidence that a new nodule of hepatocellular carcinoma recurrence was not recognized by T cells obtained at the time of RFA. In conclusion, RFA treatment generates the local conditions for activating the tumor-specific T-cell response. Although this effect is not sufficient for controlling hepatocellular carcinoma, it may represent the basis for the development of an adjuvant immunotherapy in patients undergoing RFA for primary and secondary liver tumors.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalCancer Research
Volume66
Issue number2
DOIs
Publication statusPublished - Jan 15 2006

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Hepatocellular Carcinoma
Hot Temperature
T-Lymphocytes
Liver
Neoplasms
Tumor-Associated Carbohydrate Antigens
Tumor Escape
Enzyme-Linked Immunospot Assay
Antigens
Recurrence
Tetanus Toxoid
Natural Killer T-Cells
Neoplasm Antigens
Therapeutics
Immunotherapy
Blood Cells
Proteins
Necrosis
Staining and Labeling
Escherichia coli

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. / Zerbini, Alessandro; Pilli, Massimo; Penna, Amalia; Pelosi, Guido; Schianchi, Claudia; Molinari, Atim; Schivazappa, Simona; Zibera, Carlo; Fagnoni, Francesco F.; Ferrari, Carlo; Missale, Gabriele.

In: Cancer Research, Vol. 66, No. 2, 15.01.2006, p. 1139-1146.

Research output: Contribution to journalArticle

Zerbini, A, Pilli, M, Penna, A, Pelosi, G, Schianchi, C, Molinari, A, Schivazappa, S, Zibera, C, Fagnoni, FF, Ferrari, C & Missale, G 2006, 'Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses', Cancer Research, vol. 66, no. 2, pp. 1139-1146. https://doi.org/10.1158/0008-5472.CAN-05-2244
Zerbini, Alessandro ; Pilli, Massimo ; Penna, Amalia ; Pelosi, Guido ; Schianchi, Claudia ; Molinari, Atim ; Schivazappa, Simona ; Zibera, Carlo ; Fagnoni, Francesco F. ; Ferrari, Carlo ; Missale, Gabriele. / Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. In: Cancer Research. 2006 ; Vol. 66, No. 2. pp. 1139-1146.
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