Activation of Tumor-specific T Lymphocytes After Laser-induced Thermotherapy in Patients with Colorectal Liver Metastases

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2009 Feb 3

PMID 19184001

Citations 15

Authors

Thomas Josef Vogl

Thaddaus T Wissniowski

Nagy N N Naguib

Renate M Hammerstingl

Martin G Mack

Sabine Munch

Matthias Ocker

Deike Strobel

Eckhart G Hahn

Johannes Hansler

Affiliations

Soon will be listed here.

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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