Monocyte invasion in the 3D microenvironment of tongue Câncer cells: influences on differentiation and phenotype

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide, with a 5-year survival rate of less than 50% in advanced cases. Macrophages are antigen-presenting cells and their profile of inflammatory cytokine secretion is determined by stimuli present in the microenvironment. Macrophages are present in large numbers inside solid tumors (TAMs, tumor-associated macrophages), where they can represent up to 50% of the tumor mass. The amount of TAMs is inversely related to prognosis in oral cavity squamous cell carcinoma (OSCC). Secreted products by OSCC cells increase macrophage migration/chemotaxis, indicating that the microenvironment in these tumors actively recruits macrophages. Macrophage polarization is also induced by characteristics and stimuli of the tumor microenvironment. 3D cell culture mimics important physiological features of the tumor microenvironment; therefore, it is possible to study the invasion and alteration of the monocyte/macrophage phenotype in a microenvironment closer to what occurs in vivo. Thus, the aim of this study is to evaluate the invasion and phenotypic alteration of monocytes in spheroids of two OSCC cell lines. The specific objectives are: (I) evaluate the invasion and spatial distribution of monocytes in 3D spheroids of OSCC cell lines by confocal microscopy and immunohistochemistry; (II) investigate the differentiation state of monocytes that invaded the spheroids by flow cytometry. (AU)