title: Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses.
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-gamma enzyme-linked immunospot assay and by intracellular IFN-gamma 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.
authors.affiliation: Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbini
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Amalia
authors.initials: A
authors.lastname: Penna
authors.forename: Guido
authors.initials: G
authors.lastname: Pelosi
authors.forename: Claudia
authors.initials: C
authors.lastname: Schianchi
authors.forename: Atim
authors.initials: A
authors.lastname: Molinari
authors.forename: Simona
authors.initials: S
authors.lastname: Schivazappa
authors.forename: Carlo
authors.initials: C
authors.lastname: Zibera
authors.forename: Francesco F
authors.initials: FF
authors.lastname: Fagnoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000601:surgery*; D017115:Catheter Ablation; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008113:Liver Neoplasms / Q000276:immunology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm