Laser induced thermal ablation of colorecttal cancer metastases to liver causes a significant tumor specific activation of lymphocytes

Local ablation is an extensively used treatment of inoperable solid liver tumors. We could recently show a clear immuno modulatory side effect with a significant activation of tumor specific T cells after radiofrequency ablation in a VX2 liver tumor model in rabbits and in patients suffering from hcc and colorectal cancer metastases to the liver.

This study provide that these putative side effects of ablation of solid malignancy in the liver can be also found after LiTT of colorectal cancer metastases to the liver.

Materials and methods: 11 patients with liver metastases of colorectal cancer underwent LITT. Blood was sampled before and after LITT. Test antigens were autologous liver and tumor lysate obtained from each patient. Peripheral T cell activation was assessed by an interferon gamma (IFNg) secretion assay and flow cytometry. To assess cytolytic activity, T cells were co-incubated with CaCo and release of cytosolic adenylate kinase was measured by a luciferase assay.

Results: 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 increased to 92.09 (±0.003) for CD3+ (p<0,001), 42.82 (±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 nonmalignant normal liver tissue at all time points.

Before LITT cytolytic activity against the respective cancer cells was low with RLU=1493 (±1954.68) and after LITT the cytolytic activity increased to RLU=7260 (±3929.76 [p<0,1]).

Discussion:

• Not only RFA but also LiTT seems to activate the immune system specifically towards solid tumors

• LiTT can generate an inflammatory environment for the recruitment of tumor specific T cells

• These effects should be exploited in new multimodal anti tumor therapies