||Analysis of Underlying Mechanisms for Combination Therapy of Carbon-ion Irradiation and Dendritic Cell Immunotherapy
Ma, Liqiu ,
Ando, Ken ,
Irie, Daisuke ,
Sato, Katsutoshi ,
Imai, TakashiShimokawa, Takashi
Carbon-ion (C-ion) radiotherapy (RT) is an advanced effective RT in tumors that are difficult to be cured by conventional RT due to its biological properties and excellent dose distribution. Although C-ion radiotherapy has shown good outcomes, metastasis control is an important matter as with any type of cancer treatment. There are some reports that C-ion irradiation tends to suppress metastasis or relevant abilities at in vitro and in vivo models. However, the underlying mechanisms are still not clearly understood. To improve C-ion RT, we aimed to find an optimal combination therapy for C-ion radiotherapy to prevent distant metastasis. In this study, we evaluated dendritic cells (DCs) immunotherapy, as a partner for C-ion radiotherapy. We used mouse allograft models using four mouse cancer cell lines (NR-S1, LM8, LLC and Colon26) and three mouse strains (C3H/He, C57BL/6J and BALB/c) under conditions that there were no significant effects on growth of transplanted tumor by the C-ion treatments. In NR-S1 or LM8 grafted C3H/He and LLC grafted C57BL/6J models, the number of lung metastasis was significantly decreased by the combined therapy. However, Colon26 grafted BALB/c model did not show the enhancement of metastasis inhibition by the combination treatment. To clarify the mechanisms behind the model difference, we investigated further by comparing LLC grafted C57BL/6J and Colon26 grafted BALB/c models. Dual legs grafted-one leg C-ion irradiation assay clearly demonstrated that local C-ion treatment was able to repress lung metastasis from distal non-irradiated tumor in both models. In contrast, in vitro co-culture assay indicated that C-ion irradiated Colon26 cells were not able to activate iDCs into the mature DCs, whereas LLC cells could. These results indicate that C-ion local irradiation by itself has strong ability to activate metastasis inhibition in the whole body, and genetic background or/and cancer cell type may have potent impact on the efficiency of the combination therapy.
15th International Congress of Radiation Research (ICRR 2015)