Role of M-CSF in the secretome of tongue squamous cell carcinoma cells on macrophage phenotype

Abstract

Macrophages are innate immune cells that are prototypical antigen-presenting cells and, thus, also participate in the activation of adaptive immunity. These cells are highly responsive to external stimuli and can assume a phenotype in a spectrum between two extremes: M1/classical/pro-inflammatory, characterized by high production of IL-1, IL-12 and TNF; and M2/alternative/anti-inflammatory characterized by productions of IL1-ra, IL-10 and TGF-b. The relevance of macrophages in the tumor microenvironment (TME) of oral squamous cell carcinomas (OSCC) derive from its relative abundance, representing up to 50% of the tumor mass; and also from the inverse correlation between macrophage infiltrate and prognosis and disease survival. In the TME, macrophages are known as tumor-associated macrophages (TAM) and their phenotype is determined by molecules in the TME, especially neoplastic cell-secreted products. This study intends to determine the relative contribution of neoplastic cell-secreted macrophage colony-stimulating factor (M-CSF) on the phenotype of macrophages. Macrophages differentiated from a human monocytic cell line, will be exposed to the secreted products from tongue SCC cell lines in the presence and absence of biochemical inhibitor of M-CSF receptor and of M-CSF neutralizing antibodies. Phenotype will be studied by flow cytometry and multiplex assay.