umors use chemokine signals to draw monocytes and tissue-resident macrophages into the tumor microenvironment, where the cells become tumor-associated macrophages (TAMs). Once believed to be wholly supportive of cancerous growth, these cells also play important roles in protecting against disease.
Tumor-assisting macrophages: The M2 phenotype
TAMs can take on a variety of roles to support cancer cell survival and dissemination. Originating either from monocytes that come from bone marrow, or tissue-resident macrophages that arise during embryonic development, they can repress antitumor immunity by secreting cytokines such as IL-10, which blocks dendritic cell activation, and TGF-β, which blunts T-cell responses (1). A specific subset of TAMs that produce a protein called Tie2 can also stimulate angiogenesis through secretion of vascular endothelial growth factor (VEGF) and other molecules (2). At the same time, Tie2+ macrophages come together with cancer cells and blood vessel endothelial cells to form complexes, called tumor microenvironments of metastasis (TMEMs), that create openings in blood vessels (3). Macrophages at distant sites then help cancer cells exit blood vessels and seed new tumors (4).
© SCOTT LEIGHTON
Tumor-killing macrophages: The M1 phenotype
TAMs have the potential to aid antitumor immune responses by presenting cancer cell antigens to T cells and producing cytokines that activate dendritic cells and T cells (1). Macrophages are also experts at phagocytosing and degrading foreign cells, including cancer cells (2).
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