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Characterization of the role of tumor extracellular vesicles in tolerant tumor microenvironment through TCD4 lymphocyte modulation in oral carcinoma

Grant number: 21/03319-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2022
Effective date (End): July 31, 2024
Field of knowledge:Health Sciences - Medicine
Principal researcher:Adriana Franco Paes Leme
Grantee:Tatiane de Rossi Mazo
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
Associated research grant:18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation, AP.TEM

Abstract

Head and neck cancer is a generic term representing malignant neoplasms such as oral cavity, larynx, pharynx and paranasal sinuses, with more than 90% of cases with histological features of squamous cell carcinoma. The processes involved in carcinogenesis, such as immune system evasion and metastasis formation are among the most relevant but still poorly understood events. The communication of the tumor cells with neighboring cells and the distance, as draining lymph node, can be one of the factors that pre-determines the immunological tolerance and the tumor evolution. Among the mechanisms described, the extracellular vesicles (VEs) are directly involved in cellular communication, transporting molecules that modify the behavior of cells of the microenvironment, promoting angiogenesis, modulating cells of the immune system and consequently favoring tumor development. Modulation and maintenance of an immunosuppressive microenvironment are essential for the success and propagation of the tumor. Among the cells known to be involved in the antitumor response are cytotoxic T CD8+ cells and NK cells, but other cells of the immune system may potentiate the action of these and other cell types via the action of cytokines secreted by CD4+ T cells. T helper CD4+ cells are currently classified into 7 different subtypes, based on the profile of cytokines they secrete, with Th1, Th2, Th17 and Tregulator (Treg) being the most well characterized. Therefore, we propose to evaluate the effects of VEs derived from cell lines and biopsy of oral cancer in co-culture with CD4 + T cells, investigating the potential effects on differentiation and lymphocyte activity. To evaluate the role of tumor extracellular vesicles directly on different cells of the immune system, aiming to design the individual and collective role of these cells in the tumor microenvironment and even in a systemic way is of Paramount importance for future diagnostic approaches and therapeutics with high specificity, efficiency and safety.

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