02855-A: Repurposing Drugs to Modulate Myeloid-derived Suppressor Cells (MDSCs) in Canine Soft Tissue Sarcomas
Grant Status: Open
Abstract
This proposal addresses the need for a deeper understanding of how canine soft tissue sarcomas (STS) inhibit the anti-tumor immune response. The overarching goal is to define the effects of a particularly immunosuppressive cell type, myeloid-derived suppressor cells (MDSCs), on the host immune response within canine STSs, and to explore the ability of readily-available drugs to alter this activity. Investigators will address this goal by pursuing two objectives: 1) to define the types of immune cells and their function within the tumor and peripheral blood of dogs with STS; 2) to determine the ability of repurposed drugs (sildenafil, all-trans retinoic acid, and ranolazine) to decrease the immunosuppressive forces provided of tumor-infiltrating MDSCs in canine STS. Investigators hypothesize that MDSCs will concentrate within the canine STS tumor and will display greater immunosuppressive functions in the tumor compared to peripheral blood, and that repurposed drugs can be used to decrease the immunosuppressive activity of MDSCs. Findings will be directly translatable to future clinical trials for canine STS.
Publication(s)
Soileau, A. M., Quick, C. N., Moeller, C. E., Schaumburg, J. C., & Withers, S. S. (2022). The Effect of Arginase on Canine T-Lymphocyte Functions and its Modulation by All-Trans Retinoid Acid (ATRA) in Canine Monocyte-Derived Macrophages. Veterinary Sciences, 9(7), 374. https://doi.org/10.3390/vetsci9070374
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