AUTHOR=Ricketts Tiffany Davia , Prieto-Dominguez Nestor , Gowda Pramod Sreerama , Ubil Eric TITLE=Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.642285 DOI=10.3389/fimmu.2021.642285 ISSN=1664-3224 ABSTRACT=

Macrophages are a specialized class of innate immune cells with multifaceted roles in modulation of the inflammatory response, homeostasis, and wound healing. While developmentally derived or originating from circulating monocytes, naïve macrophages can adopt a spectrum of context-dependent activation states ranging from pro-inflammatory (classically activated, M1) to pro-wound healing (alternatively activated, M2). Tumors are known to exploit macrophage polarization states to foster a tumor-permissive milieu, particularly by skewing macrophages toward a pro-tumor (M2) phenotype. These pro-tumoral macrophages can support cancer progression by several mechanisms including immune suppression, growth factor production, promotion of angiogenesis and tissue remodeling. By preventing the adoption of this pro-tumor phenotype or reprogramming these macrophages to a more pro-inflammatory state, it may be possible to inhibit tumor growth. Here, we describe types of tumor-derived signaling that facilitate macrophage reprogramming, including paracrine signaling and activation of innate immune checkpoints. We also describe intervention strategies targeting macrophage plasticity to limit disease progression and address their implications in cancer chemo- and immunotherapy.