Abstract | AIM: 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 (IFNgamma) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNgamma to detect cytotoxic T cells. The ratio of IFNgamma positive and IFNgamma 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.
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Authors | Johannes Hansler, Thaddaus-Till Wissniowski, Detlef Schuppan, Astrid Witte, Thomas Bernatik, Eckhart-Georg Hahn, Deike Strobel |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 12
Issue 23
Pg. 3716-21
(Jun 21 2006)
ISSN: 1007-9327 [Print] United States |
PMID | 16773688
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interferon-gamma
- Adenylate Kinase
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Topics |
- Adenylate Kinase
(analysis)
- Aged
- Aged, 80 and over
- CD4-Positive T-Lymphocytes
(chemistry, physiology)
- CD8-Positive T-Lymphocytes
(chemistry, physiology)
- Carcinoma, Hepatocellular
(immunology, surgery)
- Catheter Ablation
- Coculture Techniques
- Colorectal Neoplasms
(pathology, surgery)
- Female
- Humans
- Interferon-gamma
(analysis, physiology)
- Liver Neoplasms
(immunology, secondary, surgery)
- Lymphocyte Activation
(physiology)
- Male
- Middle Aged
- Necrosis
(pathology)
- Neoplasm Metastasis
(pathology, physiopathology)
- Tumor Cells, Cultured
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