Tumor-associated macrophages in skin: How to treat their heterogeneity and plasticity

Immunosuppressive tumor-associated macrophages (TAMs) promote an immunosuppressive environment in the tumor-bearing host, together with regulatory T cells (Tregs). TAMs compose cancer stroma in skin cancers including melanomas and non-melanomas. The majority of tumor-associated macrophages (TAMs) are alternatively activated M2 macrophages that favor tumor development, and they comprise one of the main populations of inflammatory cells in skin cancers. On the other hand, TAMs could be modulated into M1-type macrophages that suppress tumor growth by stimulating and recruiting Th1 and effector cells in the tumor sites. Therefore, TAMs are a target for immunotherapy in various cancers. In this review, we discuss the definition and suppressive mechanisms of TAMs, as well as their biological activities in tumor-bearing hosts to assess potential therapeutic strategies.