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

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 anti-tumor 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 tumor-recruited 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.

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

“…TAMs can also be found near or within tumor masses. Upon activation, TAMs produce and release an array of growth factors, inflammatory mediators, and proteolytic enzymes that play a critical role in cancer progression and metastasis [14, 15]. …”

Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

“…Recently, many studies have been devoted to develop in vitro 3D culture systems, which represent a more valuable approach for improved preclinical tests, providing integrated analyses of the antitumor efficacy of PDT and PDT-induced immune response in situ . These techniques include tumor spheroid formation in scaffolds or hydrogel systems, tumor cell aggregates formation by hanging-drop [ 112 ] or bioprinting techniques [ 113 ], and tumor tissue growth in microfluidics system [ 114 ]. In our previous study, we have developed an in vitro 3D breast tumor tissue model by coculturing tumor cells with stromal cells of human origin in the microfluidic system and utilized this model to evaluate the efficiency of PDT under various conditions.…”

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

“…An important role of immunomodulatory enzymes such as Arg1 or inducible nitric oxide synthases (iNOS) as well as myeloid cells in the shaping of PDT-treated tumor environment has been recently highlighted [14,15]. In this study, we analyzed the expression of enzymes: IDO, Arg1 and iNOS to elucidate the immunosuppressive mechanism induced by PDT.…”