The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma

Takahiro Shimizu, Yasushi Fuchimoto, Kazumasa Fukuda, Hajime Okita, Yuko Kitagawa, Tatsuo Kuroda

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2047-2050
Number of pages4
JournalJournal of Pediatric Surgery
Issue number12
Publication statusPublished - 2017 Dec


  • Immune checkpoint inhibitors
  • Lung metastasis
  • OX40
  • Osteosarcoma
  • PD-1/PD-L1

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health


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