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

World J Gastroenterol. 2006 Jun 21;12(23):3716-21. doi: 10.3748/wjg.v12.i23.3716.


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 (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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / analysis
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / physiology*
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / surgery*
  • Catheter Ablation*
  • Coculture Techniques
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Female
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / physiology
  • 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


  • Interferon-gamma
  • Adenylate Kinase