論文 - 詳細
| RRC ID | 68634 |
|---|---|
| 著者 | Ma L, Sakamoto Y, Ando K, Fujita H, Takahashi A, Takeshima T, Otsuka H, Ebner DK, Kakimi K, Imai T, Shimokawa T. |
| タイトル | Th Balance-Related Host Genetic Background Affects the Therapeutic Effects of Combining Carbon-Ion Radiation Therapy With Dendritic Cell Immunotherapy. |
| ジャーナル | Int J Radiat Oncol Biol Phys |
| Abstract |
PURPOSE:The goal of this study is to clarify the underlying mechanisms of metastasis suppression by CiDC (carbon-ion radiotherapy (CIRT) combined with immature dendritic cell (iDC) immunotherapy), which was previously shown to significantly suppress pulmonary metastasis in a NR-S1-bearing C3H/He mouse model. METHODS AND MATERIALS:Mouse carcinoma cell lines (LLC, LM8, Colon-26 and Colon-26MGS) were grafted into the right hind paw of syngeneic mice (C57BL/6J, C3H/He and BALB/c). Seven days later, the tumors on the mice were locally irradiated with carbon-ions (290 MeV/n, 6 cm SOBP, 1 or 2 Gy). At 1.5 days after irradiation, bone marrow-derived immature dendritic cells were administrated intravenously into a subset of the mice. The number of lung metastases was evaluated within three weeks after irradiation. In vitro cultured cancer cells were irradiated with carbon-ion (290 MeV/n, mono-energy, LET approximately 70 ∼ 80 keV/µm), and then co-cultured with iDCs for three days to determine the DC maturation. RESULTS:CiDC effectively repressed distant lung metastases in cancer cell (LLC and LM8)-bearing C57BL/6J and C3H/He mouse models. However, Colon-26 and Colon-26MGS-bearing BALB/c models did not show enhancement of metastasis suppression by combination treatment. This was further evaluated by comparing LM8-bearing C3H/He and LLC-bearing C57BL/6J models with a Colon-26-bearing BALB/c model. In vitro co-culture assays demonstrated that all irradiated cell lines were able to activate C3H/He or C57BL/6J-derived iDCs into mature DCs, but not BALB/c-derived iDCs. CONCLUSION:The genetic background of the host may have a strong impact on the potency of combination therapy. Future animal and clinical testing should evaluate host genetic factors when evaluating treatment efficacy. |
| 巻・号 | 112(3) |
| ページ | 780-789 |
| 公開日 | 2022-3-1 |
| DOI | 10.1016/j.ijrobp.2021.10.141 |
| PII | S0360-3016(21)03051-0 |
| PMID | 34740767 |
| MeSH | Animals Carbon Dendritic Cells Genetic Background Immunotherapy* Lung Neoplasms* / genetics Lung Neoplasms* / radiotherapy Mice Mice, Inbred C3H Mice, Inbred C57BL |
| IF | 5.859 |
| リソース情報 | |
| ヒト・動物細胞 | Colon-26(RCB2657) |