The Monocyte, a Maestro in the Tumor Microenvironment (TME) of Breast Cancer

SIMPLE SUMMARY: Breast cancer is one of the most prevalent cancers worldwide, surpassing lung cancer as the leading cause of overall cancer incidence. Available possible treatments nowadays include chemotherapy, hormonal therapy, and HER2-targeted therapy. Chemotherapy is notorious for its severe adverse effects. On the other hand, hormonal and HER2-targeted therapies only cover a narrow range of breast cancer subtypes. Accordingly, it is important to shed light on other therapy options. For this reason, immunotherapy nowadays is one of the most important research topics. It can be accomplished either by enhancing the pro-inflammatory immunity or suppressing the anti-inflammatory immunity. This review article aims to shed light on the importance of monocytes in the TME of breast cancer. The review also aims to highlight the behavior of the monocyte-derived populations, especially the anti-inflammatory populations. Thus, suppressing this anti-inflammatory activity might have a remarkable impact on future immunotherapy research. ABSTRACT: Breast cancer (BC) is well-known for being a leading cause of death worldwide. It is classified molecularly into luminal A, luminal B HER2−, luminal B HER2+, HER2+, and triple-negative breast cancer (TNBC). These subtypes differ in their prognosis; thus, understanding the tumor microenvironment (TME) makes new treatment strategies possible. The TME contains populations that exhibit anti-tumorigenic actions such as tumor-associated eosinophils. Moreover, it contains pro-tumorigenic populations such as tumor-associated neutrophils (TANs), or monocyte-derived populations. The monocyte-derived populations are tumor-associated macrophages (TAMs) and MDSCs. Thus, a monocyte can be considered a maestro within the TME. Moreover, the expansion of monocytes in the TME depends on many factors such as the BC stage, the presence of macrophage colony-stimulating factor (M-CSF), and the presence of some chemoattractants. After expansion, monocytes can differentiate into pro-inflammatory populations such as M1 macrophages or anti-inflammatory populations such as M2 macrophages according to the nature of cytokines present in the TME. Differentiation to TAMs depends on various factors such as the BC subtype, the presence of anti-inflammatory cytokines, and epigenetic factors. Furthermore, TAMs and MDSCs not only have a role in tumor progression but also are key players in metastasis. Thus, understanding the monocytes further can introduce new target therapies.