1. Combining Carbon ion Radiotherapy and Local Injection of Alpha-galactosylceramide-pulsed Dendritic Cells Inhibits Lung Metastases in an in vivo Murine Model
- Author
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Ohkubo, Yu, Iwakawa, Mayumi, Seino, Ken-ichiro, Nakawatari, Miyako, Wada, Haruka, Kamijuku, Hajime, Nakamura, Etsuko, Nakano, Takashi, and Imai, Takashi
- Abstract
Purpose: Our previous report indicated that carbon ion beam irradiation upregulated immunogenic, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of a local combination therapy of carbon-ion radiotherapy and immunotherapy was examined using in vivo murine model. Methods and Materials: Tumors of the mouse squamous cell carcinoma (NR-S1) cells inoculated in the leg of C3H/HeMsNrs mice were locally irradiated with a single 6 Gy dosage of carbon ions (290 MeV/nucleon, 6 cm spread-out Bragg peak). Thirty-six hours after irradiation, alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells (DCs) were injected into the leg tumor. The effects on distant lung metastases were investigated using pathological observations and immunohistochemistry. Results: The mice in the control group, which were not irradiated and not injected with alpha-GalCerpulsed DCs, had 168 +/- 53.8 metastatic nodules in their lungs at 2 weeks. The lung metastases were significantly decreased in the mouse which received the combination therapy, and the mean number of lung metastatic nodules was 2.6 +/- 1.9 (P = 0.009). In addition, the size of each lung metastasis was significantly decreased in compared to the control group (P = 0.009). Immunohistochemistry showed that ICAM-1, which activates DCs, was highly expressed on the local tumors of the carbon ionirradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased in the combination therapy group. Conclusion: The combination of carbon ion radiotherapy with the injection of alpha-GalCer-pulsed DCs into the primary tumors significantly decreased the number of lung metastases.
- Published
- 2010