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Determination of dendritic cells of regulatory profile in the tumor microenvironment and its reprogramming with immunomodulators: study in canine melanoma

Abstract

The tumor microenvironment consists of various cell types, including cells of the immune system. In particular, dendritic cells (DCs) have been widely studied in the tumor microenvironment, since these cells are considered the most potent antigen presenting cells (APCs) and are responsible for coordinating the adaptive immune response and play a key role in inducing and maintaining the antitumor immunity. DCs, however, are also subject to immune dysfunctions generated in the tumor microenvironment, and may acquire the phenotype and function of cells immunosuppressive/tolerogenic, known as regulatory DCs (regDCs) which limit activity of effector T cells (CD8+) and support tumor growth and progression. Thus, the steps in this study have the following aims: 1) Clinical Phase: correlate the clinical staging of dogs with spontaneous melanoma (oral and digital region) and the frequency of regDCs present in the tumor microenvironment by flow cytometry; 2) Experimental Ex vivo step: a) determining the phenotypic and functional profile of dendritic cells generated from blood monocytes in a tumor microenvironment (canine tumor cells from melanoma); b) evaluate the function of DCs in the presence of tumor cells by measuring cytokine and aloestimulatory activity of CD8+ and, finally, c) checking the capability to reprogram the DCs generated from blood monocytes in the presence of tumor cells by means of in vitro treatment with an activator of Rho GTPases via and a TLR-7 (Toll-like receptor-7) ligand, respectively, paclitaxel and imiquimod. The expected outcome of this project is investigate the immunobiology of canine DCs modulated by tumor aimed at the new prospects for the development of therapies for canine oral malignant melanoma. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JÉSSICA S. GARCIA; NICOLLE G.T.Q. HAZARBASSANOV; JÚLIA C. NAKAMURA; VICTOR NOWOSH; BRUNO COGLIATI; LILIAN ROSE MARQUES DE SÁ; CRISTINA O. MASSOCO. Avaliação da expressão das galectinas 1 e 3 no melanoma canino. Pesquisa Veterinária Brasileira, v. 40, n. 12, p. 1010-1017, . (15/14758-8)

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