Melanoma-associated macrophages-from molecular signals to therapeutic application

Abstract

Macrophages are an important component of the innate immune system. They are abbreviated as Mφ, MΦ, or MP. The name is derived from Greek: large eaters, μακρóς (makrós) = large, φαγεῖν (phagein) = to eat, because they engulf and digest pathogens. Tumor-associated macrophages (TAMs) are associated with drug resistance in cancers, including melanoma, and targeting them may improve cancer treatment. The purpose of this article is to examine the role of TAMs in cancer, particularly in melanoma. The relationship between TAM and treatment resistance and their potential application in the treatment of melanoma are discussed. A literature search in PubMed and Google Scholar databases for TAM and melanoma was performed. Clinical trials were searched via clinicaltrials.gov and graphical representations were created using BioRender. In melanoma, macrophages are among the most abundant immune cells in the tumor microenvironment (TME). TAMs are associated with poor prognosis and resistance. They are involved in tumorigenesis and metastasis development. M2 is the predominant type of TAM and the M2 markers CD163 and CD204 are unfavorable prognostic biomarkers. Therapeutic approaches aim to decrease their recruitment, modulate their function, or reprogram them. Treatment using chimeric antigen receptor (CAR)-M cells and nanoparticles are currently being investigated. Drugs being tested for melanoma include signal transducer and activator of transcription 3 (STAT3) inhibitors, macrophage colony-stimulating factor (M-CSF) antagonists, interferons (IFN), talimogene laherparepvec (TVEC), histone deacetylase (HDAC) inhibitors, indoleamine 2,3-dioxygenase (IDO) inhibitors, colony-stimulating factor1 receptor (CSF-1R) antagonists, CD40 agonists, arginase1 (ARG-1) inhibitors, and phosphoinositide 3‑kinase γ (PI3K-γ) inhibitors. TAMs participate in developing resistance to current melanoma therapies. Treatment directed against them may help reduce the development of resistance and improve survival.