The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma
| Autor: | Hajime Okita, Yasushi Fuchimoto, Kazumasa Fukuda, Takahiro Shimizu, Tatsuo Kuroda, Yuko Kitagawa |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Pathology medicine.medical_specialty Lung Neoplasms Programmed Cell Death 1 Receptor OX40 Ligand Kaplan-Meier Estimate B7-H1 Antigen Lesion 03 medical and health sciences Mice 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Survival analysis Mice Inbred C3H Osteosarcoma Lung Membrane Glycoproteins biology business.industry Antibodies Monoclonal General Medicine medicine.disease Prognosis Primary tumor Isotype Immunohistochemistry Transplantation Disease Models Animal medicine.anatomical_structure 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health biology.protein Surgery Tumor Necrosis Factor Inhibitors Immunotherapy Antibody medicine.symptom business Tomography X-Ray Computed Neoplasm Transplantation 030215 immunology |
| Zdroj: | Journal of pediatric surgery. 52(12) |
| ISSN: | 1531-5037 |
| Popis: | Background/purpose The prognosis of patients with metastases remains unsatisfactory in certain pediatric solid tumors. In this study, we evaluated the efficacy of immune checkpoint inhibitors against such metastases using a murine model of osteosarcoma. Methods Murine osteosarcoma LM8 cells were transplanted subcutaneously into C3H mice. The primary tumor lesion was surgically resected 11 days after transplantation. Two hundred micrograms of three antibodies (anti-PD-1, anti-PD-L1, and anti-OX-86) or an isotype antibody were administered intraperitoneally on post-transplantation days 11, 14, 18, and 21. Survival curves were plotted by the Kaplan-Meier method and compared with the log-rank test. Computed tomography (CT) scans were performed on day 11 after tumor transplantation (pre-therapy) and on day 25 (post-therapy). For pathology, 3 mice from each group were euthanized on days 11, 22, and 33 after tumor transplantation. Results The antibody-treated group had a significantly longer survival time compared with the control group (p = 0.002). Both the CT scan and pathological results revealed suppression of metastatic tumor proliferation in the treatment group as compared with the control group. Conclusions These results suggest that immune checkpoint inhibitors may be an innovative therapy for lung metastases of advanced pediatric solid tumors. |
| Databáze: | OpenAIRE |
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