Intravenous dendritic cell administration enhances suppression of lung metastasis induced by carbon-ion irradiation.
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 in the anti-tumor immune system. However, the mechanisms underlying the combination therapy of DCs and radiotherapy have been 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 treated with CIRT or PBRT, using biologically equivalent doses. Subsequently, DCs were administered intratumorally (IT) or intravenously (IV). IV and IT DC administrations combined with CIRT to the local tumor, but not alone, significantly suppressed pulmonary metastasis, whereas the combination of DCs with PBRT suppressed metastasis at a relatively higher dose. Additionally, the anti-metastatic effect was greater in IV DC administration compared with in IT DC administration in both CIRT and PBRT. The expression levels 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 with those of a PBRT-treated tumor. Taken together, these results suggest that local CIRT combined with IV DCs augments an immunogenicity of the tumor cells by ecto-calreticulin expression and the maturation of DCs to stimulate anti-tumor immunity to decrease lung metastases.
Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.|Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Ken
K
Ando
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Hidetoshi
H
Fujita
Department of Immunotherapeutic, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan.
Akihiro
A
Hosoi
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.|Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Liqiu
L
Ma
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.|Department of Radiology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
Masaru
M
Wakatsuki
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-0815, Japan.
Ken-Ichiro
KI
Seino
Department of Immunotherapeutic, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan.
Kazuhiro
K
Kakimi
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Takashi
T
Imai
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Takashi
T
Shimokawa
Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Takashi
T
Nakano
D061605:Administration, Intravenous; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D063193:Heavy Ion Radiotherapy; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D010641:Phenotype; D017785:Photons
CD40; calreticulin; carbon-ion radiotherapy; dendritic cell; metastasis