論文 - 詳細
| RRC ID | 58647 |
|---|---|
| 著者 | Takahashi Y, Yasui T, Tamari K, Minami K, Otani K, Isohashi F, Seo Y, Kambe R, Koizumi M, Ogawa K. |
| タイトル | Radiation enhanced the local and distant anti-tumor efficacy in dual immune checkpoint blockade therapy in osteosarcoma. |
| ジャーナル | PLoS One |
| Abstract |
Radiation therapy has been long utilized as localized cancer treatment. Recent studies have also demonstrated that it has a distant effect by the enhanced immunity, but it rarely occurs. The purpose of this study was to investigate whether X-ray irradiation combined with anti-PD-L1 and anti-CTLA-4 antibodies (P1C4) provides a higher probability of this distant effect as well as enhanced local antitumor efficacy for osteosarcoma. LM8 mouse osteosarcoma cells were inoculated into both legs of C3H mice assigned to one of four groups, namely no treatment (No Tx), P1C4, X-ray irradiation (RAD) to the leg of one side, and combination (COMB) groups. Survival and treatment-related immune molecular changes were analyzed. Administration of P1C4 produced a tumor growth delay on day 30 in 18% of the mice. In contrast, combination therapy produced the strongest tumor growth inhibition not only at the irradiated tumor but also at unirradiated tumor in 67% of the mice. Accordingly, lung metastasis in the COMB group was strongly reduced by 98%, with a significant survival benefit. Unirradiated tumor in mice in the COMB group significantly recruited CD8 + tumor-infiltrating lymphocytes with a moderate reduction of Treg, producing a significant increase in the CD8/Treg ratio. These results suggest that radiation enhances the efficacy of P1C4 treatment against distant metastasis as well as local control in osteosarcoma. Our data suggest that radiation therapy combined with dual checkpoint blockade may be a promising therapeutic option for osteosarcoma. |
| 巻・号 | 12(12) |
| ページ | e0189697 |
| 公開日 | 2017-1-1 |
| DOI | 10.1371/journal.pone.0189697 |
| PII | PONE-D-17-15163 |
| PMID | 29253865 |
| PMC | PMC5734786 |
| MeSH | Animals Antibodies, Monoclonal / immunology Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Bone Neoplasms / radiotherapy* CD8-Positive T-Lymphocytes / cytology Cell Cycle Checkpoints / drug effects Cell Line, Tumor Lung Neoplasms / secondary Lymphocytes / cytology Lymphocytes, Tumor-Infiltrating / drug effects Mice Mice, Inbred C3H Neoplasm Metastasis Osteosarcoma / radiotherapy* Spleen / metabolism T-Lymphocytes, Regulatory / immunology |
| IF | 4.011 |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LM8(RCB1450) |