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

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Abstract

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).

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Authors and Affiliations

  1. Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Thomas Josef Vogl, Nagy N. N. Naguib, Renate M. Hammerstingl & Martin G. Mack

  2. Department of Medicine 1, Friedrich Alexander University, Erlangen Nuremberg, Germany

    Thaddäus T. Wissniowski, Sabine Münch, Matthias Ocker, Deike Strobel, Eckhart G. Hahn & Johannes Hänsler

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  1. Thomas Josef Vogl
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  2. Thaddäus T. Wissniowski
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  3. Nagy N. N. Naguib
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  4. Renate M. Hammerstingl
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  5. Martin G. Mack
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  6. Sabine Münch
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  7. Matthias Ocker
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  8. Deike Strobel
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  9. Eckhart G. Hahn
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  10. Johannes Hänsler
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Correspondence to Thomas Josef Vogl.

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Vogl, T.J., Wissniowski, T.T., Naguib, N.N.N. et al. Activation of tumor-specific T lymphocytes after laser-induced thermotherapy in patients with colorectal liver metastases. Cancer Immunol Immunother 58, 1557–1563 (2009). https://doi.org/10.1007/s00262-009-0663-1

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  • DOI: https://doi.org/10.1007/s00262-009-0663-1

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