Understanding T regulatory cell mediated regulation of tumor fighting NK cells in a novel murine model of lung cancer

• Grant number: 15/21979-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): July 22, 2016
• Effective date (End): July 12, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Sophie Françoise Mauricette Derchain
• Grantee: Rodrigo Fernandes da Silva
• Supervisor: Silke Paust
• Host Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Baylor College of Medicine, United States
• Associated to the scholarship: 14/07401-3 - Interaction of T-reg and NK lymphocytes from ovarian cancer patients during cytotoxic activity against ovarian neoplasia, BP.DR

Abstract

Natural Killer cells are cytotoxic lymphocytes that are part of the innate immune response against viral infections and neoplasia. Recently, we have demonstrated that it is possible to obtain preparations of effector cells rich in NK cells from patients with ovarian neoplasia, by long-term culture of peripheral blood mononuclear cells (PBMC) in vitro. The effector cells obtained had a significant greater proportion of functional NK cells than the usual LAK cells (lymphokine activated killer) preparations. Additionally we observed a significant increase in the expression of various activating receptors on NK cells, including the DNAM-1, which is often decreased on NK cells of patients with malignant ovarian neoplasia. However, our preliminary data also indicates that the expansion of effector cells from ovarian cancer patients usually expands regulatory T lymphocytes (T-reg), which modulate the anti-tumor function of NK cells. Indeed, T-reg have been identified to play a role in mechanisms of immunosuppression against tumors, including ovarian cancer. In general, the presence of T-reg cells in tumor infiltrated lymphocytes and the production of the cytokines TGF-² and IL-10 are associated with worse prognosis. However, the specific mechanisms by which T-reg lymphocytes modulate the anti-tumor function of NK cells is currently poorly understood. Thus, this study aims explore the effects and consequences of T-reg mediated regulation of NK cell-mediated tumor immune-surveillance and tumor-specific immunity in a novel murine model of cigarette-smoke induced lung adenocarcinoma. (AU)