Journal Article Intravenous dendritic cell-administration enhances suppression of lung metastasis induced by carbon-ion irradiation

安藤, 謙  ,  藤田, 英俊  ,  Hosoi, Akihiko  ,  馬, 立秋  ,  若月, 優  ,  Ken-ichiro, Seino  ,  Kakimi, Kazuhiro  ,  今井, 高志  ,  下川, 卓志  ,  Nakano, Takashi

58 ( 4 )  , pp.446 - 455 , 2017-06 , Oxford academic
Carbon-ion radiotherapy (CIRT) is an advanced radiotherapy and has achieved good local control, even in tumors that are resistant to conventional photon beam radiotherapy (PBRT). However, distant metastasis control is an important issue. Recently, the combination of radiotherapy and immunotherapy has attracted the attention. In immunotherapy, dendritic cells (DCs) play a pivotal role of antitumor immune system. However, the mechanisms underlying the combination therapy of DCs and radiotherapy were unclear. In the present study, we evaluated anti-metastatic effects of this combination therapy focused on the irradiation type and the route of DC administration using a mouse model. C3H/He mice bearing NR-S1 cells were locally treated with CIRT or PBRT using biologically equivalent doses. Subsequently, DCs were administrated intratumorally (IT) or intravenously (IV). IV and IT DC-administrations (IV-DC, IT-DC) combined with CIRT to local tumor, but not alone, significantly suppressed pulmonary metastasis, whereas combination of DCs with PBRT did not suppress metastasis in the examined dose. Additionally, the anti-metastatic effect was greater in IV-DC compared to IT-DC. The expression level of CD40 and IL-12 in DCs were significantly increased after co-culturing with CIRT treated NR-S1 cells. In addition, IV-administration of those co-cultured DCs significantly suppressed pulmonary metastasis. Furthermore, ecto-Calreticulin levels from CIRT treated NR-S1 cells significantly increased compared to those of PBRT treated tumor. Taken together, these results suggest that local CIRT combined with IV-DC augments an immunogenicity of the tumor cells by ecto-Calreticulin expression and the maturation of DCs to stimulate antitumor immunity to decrease lung metastases.

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