Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 21, 2006; 12(23): 3716-3721
Published online Jun 21, 2006. doi: 10.3748/wjg.v12.i23.3716
Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases
Johannes Hänsler, Thaddäus Till Wissniowski, Detlef Schuppan, Astrid Witte, Thomas Bernatik, Eckhart Georg Hahn, Deike Strobel
Johannes Hänsler, Thaddäus Till Wissniowski, Thomas Bernatik, Eckhart Georg Hahn, Deike Strobel, Department of Medicine 1, Friedrich Alexander University, Erlangen Nuremberg, Germany
Thaddäus Till Wissniowski, Experimental Hepatology and Oncology, Nikolaus Fiebiger Center, Friedrich Alexander University, Erlangen Nuremberg, Germany
Detlef Schuppan, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
Co-first-authors: Thaddäus Till Wissniowski
Supported by the Bavarian Ministry of Economy (Leitprojekt Medizintechnik) and the Hans Löwel Foundation, Bamberg, Germany
Correspondence to: Dr. Thaddäus Till Wissniowski, Department of Medicine 1, Ulmenweg 18, 91054 Erlangen, Germany. till.wissniowski@med1.imed.uni-erlangen.de
Telephone: +49-9131-8535000 Fax: +49-9131-8535209
Received: October 28, 2005
Revised: October 28, 2005
Accepted: November 18, 2005
Published online: June 21, 2006
Abstract

AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA).

METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC) underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay.

RESULTS: Before RFA SI was 0.021 (± 0.006) for CD4+ and 0.022 (± 0.004) for CD8+ T cells against nonmalignant liver tissue and 0.018 (± 0.005) for CD4+ and 0.021 (± 0.004) for CD8+ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 (± 0.005) for CD4+ and 0.11 (± 0.012) for CD8+ T cells against HCC, and to 0.115 (± 0.031) for CD4+ and 0.15 (± 0.02) for CD8+ cells for colorectal metastases (P < 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respective cancer cells was low with 2.62 (± 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was < 2% of maximum release in all experiments.

CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8+ T cells after RFA.

Keywords: CD4; CD8; Cytotoxic; Immune response; Immunology; Immunotherapy; Interferon gamma; T cells; NK; Therapeutic vaccination