M2-like macrophages and tumor-associated macrophages: overlapping and distinguishing properties en route to a safe therapeutic potential

Ofer Guttman, Eli C. Lewis
2016 Integrative Cancer Science and Therapeutics  
Macrophages are innate leukocytes ubiquitously present in nearly all tissues, and hold critical importance for tissue homeostasis, initiation and progression of immunological responses and tissue regeneration after injury. Two of the hallmarks of macrophages are variability and plasticity. Macrophages may polarize into either pro-or anti-inflammatory phenotypes (M1-like and M2-like macrophages, respectively), and various stimuli may shift their polarization across this spectrum. Typically,
more » ... um. Typically, M1-like macrophages are involved in the onset and progression of autoimmune disorders, while M2-like macrophages have been demonstrated to effectively ameliorate such disorders by inducing the resolution of inflammatory responses and driving cellular proliferation and tissue regeneration. Many of the properties of M2-like macrophages are also characteristic of tumor-associated macrophages (TAMs), which are monocyte-derived cells that are subverted by tumors into potent pro-tumor agents capable of dampening anti-tumor cytotoxicity and facilitating tumor proliferation, angiogenesis and metastatic spread. Use of M2-polarizing immunotherapy for treatment of autoimmune disorders is a novel concept that holds promise for resolution of such disorders. However, concerns may be raised regarding the safety of such approaches as they may create tumor-permissive conditions. Here, we review current knowledge regarding the role of macrophages in autoimmunity and tumor immunology, and discuss the potential benefits and caveats of M2-polarizing therapies. and facilitating antigen-specific helper T cell localization. In contrast, an anti-inflammatory profile would most commonly promote tissue maintenance, wound resolution and tissue repair, a feat commonly exerted by resident tissue macrophages upon inflammatory resolution. While pro-inflammatory macrophages are often termed M1-like and anti-inflammatory macrophages are termed M2-like, polarization towards either M1 or M2 is not binary; M1 and M2 macrophages merely represent two extremes of a continuum of activation states. The relationship between macrophages and tumor cells is intricate. Macrophages are capable of directly killing tumor cells by secretion of excessive levels of NO. Similarly, inflammatory macrophages are central in supporting cytotoxic T cell responses by presentation of tumor antigens to helper T cells and local secretion of Th1-supporting cytokines [4, 6] . By encouraging helper T cells, the environment becomes well suited for cytotoxic T cells to undertake cytotoxic killing of tumor antigen-bearing tumor cells. However, one finds that tumors do contain macrophages, and that these tumor-associated macrophages (TAMs) are in fact central for tumor survival. TAMs may dampen anti-tumor immune activity, as well as secrete Guttman O (2016) M2-like macrophages and tumor-associated macrophages: overlapping and distinguishing properties en route to a safe therapeutic potential Volume 3(5): 554-561
doi:10.15761/icst.1000205 fatcat:jz3ee3rlvzarrofgncko4oshue