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Updated: Oct 28, 2025
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Endogenous retrovirus envelope as a tumor-associated immunotherapeutic target in murine osteosarcoma
Mary Frances Wedekind1,2, Katherine E Miller3, Chun-Yu Chen1
1Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, 700 Children's Drive Columbus, OH 43205, USA.
Abstract:
Osteosarcoma remains one of the deadliest cancers in pediatrics and young adults. We administered two types of immunotherapies, oncolytic virotherapy and immune checkpoint inhibition, to two murine osteosarcoma models and observed divergent results. Mice bearing F420 showed no response, whereas those with K7M2 showed prolonged survival in response to combination therapy. K7M2 had higher expression of immune-related genes and higher baseline immune cell infiltrates, but there were no significant differences in tumor mutational burden or predicted MHC class I binding of nonsynonymous mutations. Instead, we found several mouse endogenous retrovirus sequences highly expressed in K7M2 compared with F420. T cell tetramer staining for one of them, gp70, was detected in mice with K7M2 but not F420, suggesting that endogenous retrovirus proteins are targets for the anti-tumor immune reaction. Given prior observations of endogenous retrovirus expression in human osteosarcomas, our findings may be translatable to human disease.
Insights
Immunotherapy combination showed varied efficacy in osteosarcoma mouse models. The K7M2 model responded with prolonged survival, linked to endogenous retrovirus expression, suggesting potential for human osteosarcoma treatment.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Osteosarcoma is a highly lethal cancer in young individuals.
- Current treatments have limited efficacy, necessitating novel therapeutic strategies.
- Immunotherapy offers a promising avenue for treating osteosarcoma.
Purpose of the Study:
- To evaluate the efficacy of combined oncolytic virotherapy and immune checkpoint inhibition in osteosarcoma.
- To investigate the mechanisms underlying differential responses to immunotherapy in distinct osteosarcoma models.
- To explore the potential role of endogenous retroviruses in immunotherapy response.
Main Methods:
- Two murine osteosarcoma models (F420 and K7M2) were treated with combination immunotherapy.
- Tumor growth, survival rates, immune gene expression, and immune cell infiltration were assessed.
- Tumor mutational burden and MHC class I binding were analyzed.
- Expression of endogenous retroviruses and T cell responses were investigated.
Main Results:
- Combination immunotherapy led to prolonged survival in K7M2 model but not F420.
- K7M2 tumors exhibited higher immune gene expression and baseline immune cell infiltration.
- No significant differences in tumor mutational burden or MHC class I binding were observed.
- Highly expressed endogenous retrovirus sequences, specifically gp70, were identified in K7M2 tumors.
- T cell responses targeting endogenous retrovirus proteins were detected in responsive mice.
Conclusions:
- Differential response to immunotherapy in osteosarcoma models is linked to endogenous retrovirus expression.
- Endogenous retroviruses may serve as immunogenic targets in osteosarcoma.
- These findings suggest a potential translatable therapeutic strategy for human osteosarcoma.
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