Angiogenesis and immunosuppression in the microenvironment of canine neoplasms

• Grant number: 20/10582-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2021
• End date: November 30, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Ricardo de Francisco Strefezzi
• Grantee: Ricardo de Francisco Strefezzi
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated researchers: Adriana Tomoko Nishiya ; David John Argyle ; Heidge Fukumasu ; Juliano Coelho da Silveira ; Silvio Henrique de Freitas

Abstract

The tumour microenvironment includes neoplastic cells which are accompanied by several elements such as extracellular matrix proteins, endothelial cells, pericytes, fibroblasts and leukocytes. Their interactions may promote malignant transformation and increase the tumorigenic phenotype of cancer cells, inducing important phenomena as epithelial-mesenchymal transition, dissemination and metastasis. The literature about cancer shows that vascularization and immunosuppression are two of the most important hallmarks for tumour progression and, consequently, potential prognostic markers and therapeutic targets. The purpose of the present research project is to evaluate the relationship between tumoral angiogenesis and immunosuppression in canine cutaneous mast cell tumours (MCT) to identify novel prognostic and/or predictive markers for the disease. We will analyse the microvascular pericyte coverage index, the populations of macrophages and T lymphocytes, the expression of PD-L1 and other differentially expressed proteins between low- and high-grade MCTs, and the circulating extracellular vesicles in dogs with cutaneous MCTs. The results will be compared with consolidated prognostic markers for the disease and with the clinical course to verify their prognostic value and potential to become new therapeutic targets. (AU)