Macrophages as a Double-Edged Weapon: The Use of Macrophages in Cancer Immunotherapy and Understanding the Cross-Talk Between Macrophages and Cancer.

Macrophages (Mϕs) play an essential role in maintaining body homeostasis. They perform dual functions produced by different subtypes. Mϕs not only fight against pathogens and foreign bodies such as bacteria or cancer cells but also participate in healing and repairing damaged tissue since they maintain both proinflammatory and anti-inflammatory effects sequentially. Tumors possess the ability to polarize Mϕs from proinflammatory M1 subtype to anti-inflammatory M2-like Mϕs called tumor-associated macrophages, which, in turn, help the tumors to acquire cancer hallmarks. Consequently, this polarization allows tumors to grow and spread. In this light, Mϕs have been a subject of intense study, and researchers have developed protocols to derive different Mϕs subtypes either as a new state-of-the-art therapeutic approach or to understand the cross-talk between cancer and Mϕs. In this review, we present the use of primary Mϕs in adoptive immunotherapy for cancer, illustrate the reciprocating interplay between cancer and Mϕs, and the resulting structural and functional change on both cell types. Furthermore, we summarize the recent cutting-edge approaches of using Mϕs in cancer immunotherapy.