Measurement of regulatory T cells and matrix metalloproteinase of dogs with lymphoma submitted to chemotherapy protocol Wisconsin-Madison

• Grant number: 11/12870-4
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2011
• End date: May 31, 2014
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Áureo Evangelista Santana
• Grantee: Áureo Evangelista Santana
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated researchers: Letícia Abrahão Anai ; Livia Maria Souza Semolin ; Mirela Tinucci Costa ; Thiago Demarchi Munhoz

Abstract

Lymphoma is a neoplasia characterized by malignant clonal lymphocites proliferation and originates from the bone marrow, spleen, liver and lymphnodes. However, it can practically evolve from any organ by continuous migration of lymphocites through different organic tissues. Lymphoma is one of the most common malignancies in dogs, accounting for 8,5 to 9% of all canine tumors. T regulatory cells (Tregs) are described as T CD4+ lymphocites which express constitutively the ± chain from the interleukin 2 (IL2) receptor (CD25). It is believed that Tregs regulate the physiological immune response and is involved in a series of infectious, allergic, neoplastic and autoimmune diseases. Involvement in the immunologic process of implants has also been observed. There is evidence that the Tregs subregulate the effective function against tumors, resulting in T cells disfunction in humans and dogs with cancer. A study with Tregs in humans has encouraged similar researches in veterinary medicine and despite the rising number of papers about Tregs in dogs, only a few of them were accomplished with lymphoma cases therefore little results are available. Recent studies suggest that some drugs can be used to extinguish or suppress Tregs function. The increase on the enzyme COX-2 expression by the tumor cells and local inflammatory cells stimulate the development of Tregs. Thus, the treatment with COX-2 inhibitors such as non steroidal anti-inflammatory is a way of inhibiting Tregs. Proteolytic enzymes like metalloproteinases 2 and 9, have fundamental importance in tumor progression for promoting the penetration and tissue infiltration, establishing true routes to tumor spread. Thus, it has been speculated that the increase of their expressions may be related to increased tumor progression and invasiveness, resulting in worse prognosis. Porting, the aim of this study was to quantify the regulatory T cells and the matrix metalloproteinases 2 and 9, in dogs with multicentric lymphoma, at diagnosis, after the first cycle of chemotherapy (5 weeks), last week (20th weeks) and at the time of relapse (the event) with the Madison-Wisconsin protocol of 19 weeks (MW-19). (AU)