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Updated: May 24, 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
Enhanced immune responses are accompanied by increased MAGEA expression in osteosarcoma metastases
Debora M Meijer1, Siddh van Oost2, Jessica P Roelands1
1Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
Objective:
Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20%-30%. T cell checkpoint blockade immunotherapies have revolutionised cancer treatment in the last decade, but their impact remains limited in osteosarcoma.
Methods And Analysis:
In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterisation of a unique sample set comprising 30 osteosarcoma samples from seven patients, collected throughout disease progression. We performed RNA-sequencing and imaging mass cytometry analysis on these samples to reveal the immunological landscape during osteosarcoma progression.
Results:
Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anticancer immunity were enriched in metastatic lesions as compared with primary tumours. Spatial analysis showed T cells infiltrating central regions of osteosarcoma metastases, indicating the absence of an immune excluded environment. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly melanoma antigen family A (MAGEA)-related antigens, in osteosarcoma metastases, which was validated in an independent cohort (N=91). In addition, we demonstrated the presentation of MAGE-derived peptides in three out of four osteosarcoma cell lines.
Conclusion:
These findings indicate a concurrent augmentation of cytotoxic antitumour immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation suggests the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.
Insights
Metastatic osteosarcoma shows increased T cell immunity and cancer testis antigen expression, particularly MAGEA. This suggests MAGEA antigens are promising targets for novel immunotherapies in advanced osteosarcoma treatment.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Osteosarcoma is the most common primary bone cancer.
- Metastatic disease affects 50% of patients, with poor 5-year survival rates (20-30%).
- Current immunotherapies show limited efficacy in osteosarcoma.
Purpose of the Study:
- To explore novel immunotherapeutic strategies for advanced osteosarcoma.
- To characterize the immunogenomic landscape of osteosarcoma during disease progression.
Main Methods:
- Immunogenomic characterization of 30 osteosarcoma samples from seven patients.
- RNA-sequencing and imaging mass cytometry analysis.
- Validation in an independent cohort (N=91).
Main Results:
- Enriched cytotoxic T cell-driven immunity in metastatic lesions compared to primary tumors.
- T cells infiltrated metastases, indicating no immune exclusion.
- Increased expression of cancer testis antigens, especially MAGEA, in metastases, validated independently.
- MAGE-derived peptides presented in osteosarcoma cell lines.
Conclusions:
- Cytotoxic immune responses and MAGEA antigen expression are augmented from primary to metastatic osteosarcoma.
- MAGEA antigens represent potential therapeutic targets for advanced osteosarcoma immunotherapy.
