Development of a strategy to inhibit regulatory T cells, based on blocking the traffic of regulatory T cells by RNAi, to potentiate antitumoral response.

• Grant number: 12/11480-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2013
• Effective date (End): July 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Thaís Hudari Abib
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Regulatory T cells (Tregs) have the unique property to inhibit the proliferation of T lymphocytes and play an important role in maintaining immunologic tolerance. The analysis of clinical samples isolated from tumoral sites reveals the infiltration of Treg cells and shows that the tumoral progression is correlated with the infiltrate. The traffic of regulatory T cells to tumoral sites is mediated by chemokines secreted by the tumor or immune cells located in the tumoral region, that interact with Treg receptors, like CCR4. Emerging studies suggest that it's possible to inhibit the Tregs traffic using antibodies against the CCL22 chemokine, which is the ligand of CCR4, enhancing the response to cancer therapy.Our goal is analyze the possibility to use a system based in RNA interference in order to silence genes associated with the expression of chemokine receptors in Tregs, and the expression of the respective chemokines in tumoral cells, to inhibit the Tregs traffic to tumoral sites, enhancing the tumor's detection and elimination by the immune system. We plan to test the silencing of molecular targets associated with Treg's chemotaxis, including Tregs receptors and their ligands in tumoral cells, individually or in a combined way, analyzing the best strategy to inhibit the traffic of Tregs to tumoral implantation sites.The success of this project will represent the development of strategies to inhibit Tregs in vivo in order to potentiate the antitumoral immune response, which could be used to enhance cancer therapies.