The functional profile and therapeutic approaches of the tumor associated macrophages

Abstract

Introduction. Macrophages are one of the most flexible immune cell of our body. Recent studies have elucidated their involvement in the tumour pathology too. There are two types of macrophages: M1 (pro-inflammatory) and M2 (anti-inflammatory). Macrophages that populate the tumours undergo morphologic changes and are called tumour-associated macrophages (TAM). It is assumed that these cells express a phenotype M2, which are responsible of tumorigenesis and metastases. Furthermore, TAM interact with many cells, as effector T-cell, neoplastic cells, endothelial cells, etc. Through these interactions, these cells can promote angiogenesis, metastasis, cancer cell stemness, also chemotherapeutic resistance, immunosuppressive functions. Aim of the study. This review will study the polarization states of macrophages, their functional profile and role in cancer, and therapeutic approaches of the tumour-associated macrophages. Results. Among the innate and adaptive immune cells that are involved in the tumour microenvironment, macrophages are particularly abundant and are present in all stages of tumour progression. M1-like TAM are stimulated by LPS, IFN-γ and/or GM-CSF that produces a variety of pro-inflammatory and thereby anti-tumour cytokines and chemokines. M2-like TAM are stimulated by tumour-derives like interleukines: IL-4, IL-13, IL-10, M-CSF and/or lactic acid. Consequently, M2- like TAM secrete a spectrum of anti-inflammatory and pro-tumour cytokines, chemokines and signalling molecules. Therefore, TAM could be either tumour killing (M1) or tumour promoting (M2); this data suggests that macrophages are attractive targets for improving of new combined immunotherapy to the fight cancer. Combining inhibitors that target the CCL2- CCR2 and CSF1-CSF1R reduces macrophage migration and pro-tumour activation, so this fact stops tumour growth and metastasis formation. More than that, the inhibitors supplies chemotherapeutic regimen in early phase clinical trials. Conclusions. Certainly, macrophages play an important role in tumour progression and metastasis due to the plasticity they express during activation, especially in vivo. Current approaches to cancer immunotherapy using macrophages involve multiple cytokines and chemokines that can cause immune responses. The application of these therapies have been shown to reduce tumor size and angiogenesis, recruit immune cells to the tumor site, and prevent the polarization of macrophages to an M2 phenotype.