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Updated: Aug 12, 2026
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Induction of a specific CD8+ T-cell response to cancer/testis antigens by demethylating pre-treatment against
Binghao Li1, Xiaobing Zhu2, Lingling Sun1
1Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310008, China.
Abstract:
Conventional non-surgical therapeutic regimens against osteosarcoma are subject to chemoresistance and tumor relapse, and immunotherapy may be promising for this tumor. However, it's hard to find satisfactory epitopes for immunotherapy against osteosarcoma. Cancer/testis antigens (CTAs), such as MAGE-A family and NY-ESO-1, the potential antigens that almost exclusively express in tumor cells and immune-privileged sites, have been found expressed in osteosarcoma also. Nevertheless, the expression of CTAs is downregulated in many tumors, constraining the application of immunotherapy. In this article, we demonstrate that the expression of MAGE-A family and NY-ESO-1 in osteosarcoma cells can be upregulated following treatment with demethylating agent 5-aza-2'-deoxycytidine and consequently induces a CTA specific CD8+ T-cell response against osteosarcoma in vitro and in vivo. The in vivo imaging was realized by using luciferase-transfected HOS cells and DiR labeled T-cells in severely combined immunodeficiency mouse models. Cytotoxic T cells specifically recognizing MAGE-A family and NY-ESO-1 clustered at the tumor site in mice pre-treated with DAC and resulted in tumor growth suppression, while it was not observed in mice without DAC pre-treatment. This study is important for more targeted therapeutic approaches and suggests that adoptive immunotherapy, combined with demethylating treatment, has the potential for non-surgical therapeutic strategy against osteosarcoma.
Insights
This study shows that demethylating agents can boost cancer/testis antigen expression in osteosarcoma, enhancing T-cell responses for potential immunotherapy. This approach suppressed tumor growth in mice, offering a new non-surgical strategy.
Area of Science:
- Oncology
- Immunology
- Cancer Therapeutics
Background:
- Osteosarcoma treatments face chemoresistance and relapse.
- Immunotherapy holds promise but lacks suitable osteosarcoma targets.
- Cancer/testis antigens (CTAs) are expressed in osteosarcoma but often downregulated.
Purpose of the Study:
- To investigate if demethylating agents can upregulate CTA expression in osteosarcoma.
- To evaluate the efficacy of CTA-specific CD8+ T-cell responses against osteosarcoma.
- To explore a novel immunotherapy approach combined with demethylating treatment for osteosarcoma.
Main Methods:
- Osteosarcoma cells were treated with 5-aza-2'-deoxycytidine (DAC) to upregulate CTAs.
- In vitro and in vivo experiments assessed CTA-specific CD8+ T-cell responses.
- In vivo imaging utilized luciferase-transfected HOS cells and DiR-labeled T-cells in immunodeficient mice.
Main Results:
- DAC treatment successfully upregulated MAGE-A family and NY-ESO-1 expression in osteosarcoma cells.
- CTA-specific CD8+ T-cells were induced and targeted tumor sites in vivo.
- Pre-treatment with DAC led to significant osteosarcoma tumor growth suppression in mice.
Conclusions:
- Demethylating agents can enhance osteosarcoma immunotherapy potential by increasing CTA expression.
- Adoptive immunotherapy combined with demethylating treatment shows promise for osteosarcoma.
- This strategy offers a potential non-surgical therapeutic approach for osteosarcoma.
