Targeting Macrophages as a Novel Therapy to Treat Triple-Negative Breast Cancer: A Literature Review

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive form of cancer which lacks the traditional cellular targets of other types of breast cancer. As such, it is increasingly important to find alternative targets to treat this deadly disease. Recently, tumour-associated macrophages (TAMs) have become an exciting area of focus for cancer research and may provide a source of treatment options for TNBC. Macrophages are an important part of the innate immune response and also play a crucial role in tumour progression, inflammation, and metastasis. TAMs fall along a spectrum and are generally presented as either M1 type or M2 type. M1 macrophages are considered anti-tumorigenic whereas M2 macrophages are considered pro-tumorigenic, promoting tumour growth and inhibiting T-cell response. A search of the University of Alberta’s online library database was carried out with a specific emphasis on clinical research.  Search efforts focused on the effects of macrophages on the progression of breast cancer. Further searches were performed to determine the efficacy of targeting macrophages to treat cancer. Increasing the relative ratio of M1 to M2 macrophages or depletion of macrophages may lead to a better prognosis in TNBC. TAMs may be repolarized to M1 phenotype using metformin, inhibition of SerpinE2, YAP/STAT3, or MED1/PPARy. Macrophage recruitment to the tumour microenvironment may be inhibited by targeting chemokines such as CCL2. Current methods could not efficiently deplete macrophages at such a high abundance. The abundance of macrophages and their phagocytic properties could instead be exploited to increase tumour cell phagocytosis by targeting the CD47-SIRPɑ axis. Exciting opportunities have been revealed regarding inhibition of macrophage recruitment, repolarization of M2 to M1 type, and through exploitation of phagocytic properties of macrophages. However, conflicting results can be found for all these emerging treatment strategies. Worsening matters is the lack of knowledge regarding macrophage functions and the confusing landscape of macrophages current naming conventions. As such, further research is required to determine the efficacy of macrophages as a target in breast cancer treatment.