The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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
JournalJournal of Pediatric Surgery
DOIs
Publication statusAccepted/In press - 2017

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Osteosarcoma
Neoplasm Metastasis
Lung
Transplantation
Neoplasms
Tomography
Pediatrics
Control Groups
Investigational Therapies
Survival
Inbred C3H Mouse
Antibodies
Anti-Idiotypic Antibodies
Therapeutics
Pathology

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Cite this

The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma. / Shimizu, Takahiro; Fuchimoto, Yasushi; Fukuda, Kazumasa; Okita, Hajime; Kitagawa, Yuukou; Kuroda, Tatsuo.

In: Journal of Pediatric Surgery, 2017.

Research output: Contribution to journalArticle

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AU - Fuchimoto, Yasushi

AU - Fukuda, Kazumasa

AU - Okita, Hajime

AU - Kitagawa, Yuukou

AU - Kuroda, Tatsuo

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