The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma
Takahiro Shimizu1, Yasushi Fuchimoto1, Kazumasa Fukuda2
1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
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.
Insights
Immune checkpoint inhibitors significantly improved survival in a murine osteosarcoma model, suppressing metastatic tumor growth. This suggests a promising new therapy for pediatric solid tumors with metastases.
Area of Science:
- Oncology
- Immunotherapy
- Pediatric Solid Tumors
Background:
- Prognosis for pediatric solid tumors with metastases is often poor.
- Novel therapeutic strategies are needed to combat metastatic disease.
Purpose of the Study:
- To evaluate the efficacy of immune checkpoint inhibitors (ICIs) against osteosarcoma lung metastases.
- To utilize a murine model to assess ICI treatment outcomes.
Main Methods:
- Osteosarcoma LM8 cells were implanted in mice, and primary tumors were resected.
- Mice received anti-PD-1, anti-PD-L1, or anti-OX-86 antibodies, or isotype control.
- Survival, CT scans, and pathological analyses were used to assess treatment efficacy.
Main Results:
- Antibody-treated mice exhibited significantly longer survival than controls (p = 0.002).
- CT scans and pathology confirmed suppressed metastatic tumor proliferation in the ICI-treated group.
- ICIs demonstrated efficacy in reducing metastatic burden.
Conclusions:
- Immune checkpoint inhibitors show potential as an innovative therapy for lung metastases in advanced pediatric solid tumors.
- This study supports further investigation of ICIs for pediatric metastatic cancers.
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