The cellular and molecular origin of tumor-associated macrophages

Abstract

Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an “alternatively activated” phenotype. TAM differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.

PKB/Akt-dependent regulation of inflammation in cancer

“…Tumor associated macrophages (TAMs) have been widely observed in different types of cancers and often constitute the dominant myeloid cell population in tumors [94]. During tumor initiation and malignant progression, macrophages build up bidirectional interacting networks with tumor cells and other cells of the tumor microenvironment.…”

Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development

“…enzymes, proinflammatory cytokines, regulatory factors, interleukin-12 (IL-12), and are also involved in termination of tumor cells by secreting tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), and nitrogen species (RNOS). On the contrary, type II macrophages (M2) moderate the inflammatory response, eliminate cell wastes, promote angiogenesis and tissue remodeling, and release cytokines, including anti-inflammatory interleukin-10 (IL-10) (Mariani and Edwards, 2008;Gordon, 2003;Franklin et al, 2014).…”

Delineating CSF-1-dependent regulation of myeloid cell diversity in tumors

“…4 Furthermore, while TAMs have been termed M2 or alternatively activated macrophages (AAMs), IL-4 ¡/¡ PyMT mice had normal proportions of TAMs (characterized as CD11b lo MHCII hi VCAM C cells that highly expressed itgax, the gene that encodes CD11c) and TAM differentiation was intact in the absence of lymphocytes, suggesting TAMs are not the same as classical AAMs. 9 Thus, it has been suggested that macrophage heterogeneity should not be simplified on a linear scale between M1 and M2, but should be described in terms of the diversity of points on a color wheel. 4 Future Therapy With CSF-1…”