Activation of tumor-specific T lymphocytes after laser-induced thermotherapy in patients with colorectal liver metastases

Cancer Immunol Immunother. 2009 Oct;58(10):1557-63. doi: 10.1007/s00262-009-0663-1. Epub 2009 Jan 29.


Purpose: To asses if laser-induced thermotherapy (LITT) induces a specific cytotoxic T cell response in patients treated with LITT for colorectal cancer liver metastases.

Methods: Eleven patients with liver metastases of colorectal cancer underwent LITT. Blood was sampled before and after LITT. Peripheral T cell activation was assessed by an interferon gamma (IFNg) secretion assay and flow cytometry. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. T cells were stained for CD3/CD4/CD8 and IFNg to detect activated T cells. The ratio of IFNg positive to IFNg negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human colorectal cancer cells (CaCo) and cytosolic adenylate kinase release was measured by a luciferase assay.

Results: IFNg secretion assay: before LITT SI was 12.73 (+/-4.83) for CD3+, 4.36 (+/-3.32) for CD4+ and 3.64 (+/-1.77) for CD8+ T cells against autologous tumor tissue. Four weeks after LITT SI had increased to 92.09 (+/-12.04) for CD3+ (P < 0.001), 42.92 (+/-16.68) for CD4+ (P < 0.001) and 47.54 (+/-15.68) for CD8+ T cells (P < 0.001) against autologous tumor tissue. No increased SI was observed with normal liver tissue at any time point. Cytotoxicity assay: before LITT activity against the respective cancer cells was low, with RLU = 1,493 (+/-1,954.68), whereas after LITT cytolytic activity had increased to RLU = 7,260 [+/-3,929.76 (P < 0.001)].

Conclusion: Patients with liver metastases of colorectal cancer show a tumor-specific cytotoxic T cell stimulation and a significantly increased cytolytic activity of CD3+, CD4+ and CD8+ T cells after LITT against an allogenic tumor (CaCo cell line).

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Catheter Ablation
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Hyperthermia, Induced*
  • Interferon-gamma / metabolism
  • Lasers
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / secondary
  • Lymphocyte Activation / physiology*
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes, Cytotoxic / immunology*


  • Interferon-gamma