Role of tumor cell-secreted TGF-b on macrophage phenotype

• Grant number: 19/25592-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Carlos Rossa Junior
• Grantee: Ana Lídia Pinheiro Silva
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Macrophages are the most abundant immune cell type in the tumor microenvironment (TME) of head and neck squamous cell carcinomas (HNSCC), representing up to 50% of the tumor mass. The intensity of macrophage infiltration is inversely proportional to prognosis and disease survival. In the TME, macrophages are called tumor-associated macrophages (TAM) and their phenotype is determined by molecules in the TME, including neoplastic cell-secreted products. As innate immune antigen-presenting cells, macrophages have a fundamental role in maintaining homeostasis and in the response to Physico-chemical and microbial insults. Macrophages also have an important role in immune surveillance, detecting neoplastic cells and activating the adaptive immune response for their elimination, besides participating in the repair process after treatment. The goal of this study is to determine, in vitro, the relative contribution of HNSCC cell-secreted transforming growth factor-beta (TGF-b ) on the phenotype of macrophages. We will use macrophages derived from a human monocytic cell line, which will be exposed to the secreted products from two HNSCC cell lines. The phenotype of macrophages will be studied by flow cytometry (CD80/CD163) and expression of inflammatory mediators IL-6, IL-10, TNF and MMP-9 by RT-qPCR. The relative contribution of tumor cell-secreted TGF-b will be determined by antibody-mediated depletion.