Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

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 befor...

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Bibliographic Details
Published in:World journal of gastroenterology : WJG 2006-06, Vol.12 (23), p.3716-3721
Main Authors: Hansler, Johannes, Wissniowski, Thaddaus-Till, Schuppan, Detlef, Witte, Astrid, Bernatik, Thomas, Hahn, Eckhart-Georg, Strobel, Deike
Format: Article
Language:English
Subjects:
Adenylate Kinase - analysis
Aged
Aged, 80 and over
Carcinoma, Hepatocellular - immunology
Carcinoma, Hepatocellular - surgery
Catheter Ablation
CD4-Positive T-Lymphocytes - chemistry
CD4-Positive T-Lymphocytes - physiology
CD8-Positive T-Lymphocytes - chemistry
CD8-Positive T-Lymphocytes - physiology
Coculture Techniques
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Female
Humans
Interferon-gamma - analysis
Interferon-gamma - physiology
Liver Cancer
Liver Neoplasms - immunology
Liver Neoplasms - secondary
Liver Neoplasms - surgery
Lymphocyte Activation - physiology
Male
Middle Aged
Necrosis - pathology
Neoplasm Metastasis - pathology
Neoplasm Metastasis - physiopathology
Tumor Cells, Cultured
T囊依赖性淋巴细胞
放射频率
细胞溶解
肝移植
肝细胞癌
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Summary: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 respect（ve 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.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v12.i23.3716