Contribution of resident and recruited macrophages to the photodynamic intervention of colorectal tumor microenvironment

MARÍA FLORENCIA PANSA; MARIA JULIA LAMBERTI; INGRID SOL COGNO; SILVIA GRACIELA CORREA; NATALIA BELÉN RUMIE VITTAR; VIVIANA ALICIA RIVAROLA

TUMOR BIOLOGY

KARGER

Lugar: Basel; Año: 2016 p. 1 - 12

1010-4283

Abstract The study of cellular interactions in the tumor microenvironment has become one of the main areas of research in the fight against cancer. Tumor-associated macrophages (TAMs) influence tumor progression and therapy response due to its functional plasticity. Regarding cancer treatment, photodynamic therapy (PDT) is a minimally invasive and clinically approved procedure that involves the administration of a photosensitizer (PS), a nontoxic photosensitizing drug which is selectively retained in neoplastic tissue. Here, we investigated the role of resident and nonresident macrophages in the context of a PDT-treated colorectal tumor by developing a combination of 2-D and three-dimensional (3-D) experimental platform, recreating tumor-stroma interactions in vitro. Enhancement of cytotoxicity of PDT was achieved in the presence of nonresident macrophages which had a strong antitumor phenotype mediated by the production of nitric oxide, IL-6, and tumor necrosis factor alpha (TNF-α). On the contrary, tumor resident macrophages induced a pro-tumor phenotype promoting tumor cell migration and endothelial stimulation. Due to their plasticity, tumor-resident or tumorrecruited macrophages can differentially influence the response of tumors to PDT, so their multifactorial roles should be considered in the overall design of anti-tumor therapeutic.