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


CONCLUSIONS
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).
Vogl
Thomas Josef
TJ
Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. t.vogl@em.uni-frankfurt.de
Wissniowski
Thaddäus T
TT
Naguib
Nagy N N
NN
Hammerstingl
Renate M
RM
Mack
Martin G
MG
Münch
Sabine
S
Ocker
Matthias
M
Strobel
Deike
D
Hahn
Eckhart G
EG
Hänsler
Johannes
J
D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D017115:Catheter Ablation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000378:metabolism; D007834:Lasers; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007371:Interferon-gamma