Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy
| Autor: | Stacey A. Fox-Alvarez, Elias Sayour, Rowan J. Milner, Souza Ch de Mello, Bikash Sahay, Marc E. Salute, L Powers, S. Hutchison, Amandine Lejeune, AM Livaccari, Anna Szivek |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Myeloid 040301 veterinary sciences medicine.medical_treatment Immunology Active immunotherapy Biology Melanoma Vaccine 0403 veterinary science 03 medical and health sciences Dogs Gangliosides medicine Canine Melanoma Animals Dog Diseases Melanoma Chemokine CCL2 030304 developmental biology 0303 health sciences General Veterinary Myeloid-Derived Suppressor Cells Granulocyte-Macrophage Colony-Stimulating Factor 04 agricultural and veterinary sciences Immunotherapy medicine.disease Interleukin-10 Interleukin 10 medicine.anatomical_structure Gene Expression Regulation Myeloid-derived Suppressor Cell Female |
| Zdroj: | Veterinary Immunology and Immunopathology. 216:109912 |
| ISSN: | 0165-2427 |
| Popis: | Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect