Abstract
The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated macrophages (TAMs), are contributors to many pro-tumorigenic outcomes in cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, tumor cell proliferation, and metastasis. The tumor microenvironment (TME) can influence macrophage recruitment and polarization, giving way to these pro-tumorigenic outcomes. Investigating TME-induced macrophage polarization is critical for further understanding of TAM-related pro-tumor outcomes and potential development of new therapeutic approaches. This review explores the current understanding of TME-induced macrophage polarization and the role of M2-polarized macrophages in promoting tumor progression.
Highlights
Macrophages are myeloid cells that are essential members of the innate immune response [1]
Current literature supports the theory that most tumorassociated macrophages (TAMs) originate from either tissueresident embryonic macrophages or macrophages derived from circulating monocytes that originate in the bone marrow [87]
While this has shown promise, in murine breast cancer models, a rebound effect was shown after the withdrawal of anti-CCL2 treatment, increasing the infiltration of bonemarrow monocytes into the tumor and accelerating lung metastasis [135]
Summary
Macrophages are myeloid cells that are essential members of the innate immune response [1] These heterogenous cells originate from monocyte precursors in the blood and differentiate in the presence of cytokines and growth factors in the tissues they infiltrate [2,3]. Macrophages are found in every human tissue in the body and exhibit anatomical and functional diversity [4] These cells have three key functions: phagocytosis, exogenous antigen presentation, and immunomodulation through cytokine and growth factor secretion. ANG2 secretion by blood vessels causes macrophages to upregulate WNT7B, which induces the proliferation of vascular endothelial cells and allows them to be targeted by ANG-2-induced apoptosis [13]. Macrophages secrete WNT11 and WNT5A, which induce the expression of soluble vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) in an autocrine fashion. Lymphangiogenesis can lead to tumor metastasis [19], making the role of macrophage regulation important to understand and further investigate
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