The portrayal of macrophages as tools and targets: A paradigm shift in cancer management

Macrophages play a major role in maintaining an organism's physiology, such as development, homeostasis, tissue repair, and immunity. These immune cells are known to be involved in tumor progression and modulation. Monocytes can be polarized to two types of macrophages (M1 macrophages and pro-tumor M2 macrophages). Through this article, we aim to emphasize the potential of targeting macrophages in order to improve current strategies for tumor management. Various strategies that target macrophages as a therapeutic target have been discussed along with ongoing clinical trials. We have discussed the role of macrophages in various stages of tumor progression epithelial-to-mesenchymal transition (EMT), invasion, maintaining the stability of circulating tumor cells (CTCs) in blood, and establishing a premetastatic niche along with the role of various cytokines and chemokines involved in these processes. Intriguingly macrophages can also serve as drug carriers due to their tumor tropism along the chemokine gradient. They surpass currently explored nanotherapeutics in tumor accumulation and circulation half-life. We have emphasized on macrophage-based biomimetic formulations and macrophage-hitchhiking as a strategy to effectively target tumors. We firmly believe that targeting macrophages or utilizing them as an indigenous carrier system could transform cancer management.