Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
- Poster presentation
- Open Access
- Published:
ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth
Journal for ImmunoTherapy of Cancer volume 2, Article number: P217 (2014)
Myeloid Derived Suppressor Cells (MDSCs) heavily infiltrate in a variety of solid tumors and suppress anti-tumor T-cell activity. Our recent studies have demonstrated the ability of monocytic, Ly6C+ MDSCs to promote glioma growth through the activation of cyclooxygenase (COX)-2 pathway, which is responsible for prostaglandin-synthesis. ONO-AE3-208 is an antagonist of the prostaglandin E (EP)-4 receptor, which is an important positive feedback regulator of the COX-2 pathway. We thus examined the ability of ONO-AE3-208 to suppress MDSC activity in gliomas. ONO-AE3-208 treatment in mice bearing established GL261-quad glioma in the brain resulted in complete and persistent rejection of the tumors. Flow cytometric analysis revealed that gliomas in the ONO-AE3-208-treated mice were infiltrated by fewer numbers of Ly6C+ MDSCs compared with non-treated animals. We subsequently isolated glioma-infiltrating Ly6C+ MDSCs by flow-sorting to address their functions. RT-PCR analysis revealed that the Ly6C+ MDSCs derived from ONO-AE3-208 treated mice expressed lower levels of the Arg1 and Cox2 expression compared to control animals. Consistently, brain infiltrating leukocytes in ONO-AE3-208 treated tumor-bearing mice demonstrated enhanced IFN-g expression compared with control mice, suggestive of enhanced T-cell activity. Importantly, ONO-AE3-208 inhibited glioma growth and promoted immune activity in 2 additional murine glioma models: the Sleeping Beauty de novo glioma model and the SB28 glioma cell line model. Our data demonstrate that ONO-AE3-208 may be useful in the treatment of glioma patients to suppress Ly6C+ MDSCs and promote anti-tumor immunity.
Author information
Authors and Affiliations
Rights and permissions
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
About this article
Cite this article
Kohanbash, G., Straw, E., Ahn, B. et al. ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth. j. immunotherapy cancer 2 (Suppl 3), P217 (2014). https://doi.org/10.1186/2051-1426-2-S3-P217
Published:
DOI: https://doi.org/10.1186/2051-1426-2-S3-P217
Keywords
- Cox2 Expression
- Glioma Cell Line
- Glioma Patient
- Myeloid Derive Suppressor Cell
- Cell Line Model