Table 1.

Differences between mouse and human macrophages that may impact the efficacy of antitumor strategies targeting TAM

Parameters	Murine Mφ	Human Mφ	Tumor microenvironment and human TAMs	Therapeutic implications
Roles of GM-CSF	Induces DCs and Mφ generation	Induces Mφ generation	Present in inflammatory and tumor sites Modulates the phenotype of human TAMs	M-CSF neutralization may boost the impact of GM-CSF and thereby favor DC generation in mice but not in human
Type II IFN expression	High expression	Low expression by both in vitro generated human Mφ and TAMs		Type II IFN production by murine TAMs may favor cytotoxic T lymphocyte responses and their reprogramming into antitumor Mφ
M1/M1-type versus M2/M2-type polarizing factors	M1: IFNγ+LPS	M1-type: GM-CSF, GM-CSF+IFNγ M-CSF+IFNγ	Cancers are mostly infiltrated by Th1, Th17 and Treg cells rather than Th2 cells	The M1/M2 model is not relevant for human TAM characterization
	M2: M-CSF+IL-4	M2-type: M-CSF+IL-4 (or IL-1 or IL-10)	The M1/M2 classification (based on the Th1/Th2 dichotomy) and IL-4-induced M2-like cells as a model of TAMs are poorly relevant in human cancer
M1/M1-type and M2/M2-type markers	M1: iNOS, CD80, MHC-II, IFNγ	M1-type: inflammatory cytokines (IL-1β, IL-6 and TNFα), IL-12	Human TAMs exhibit both M1 and M2 characteristics (concomitant expression of inflammatory and regulatory cytokines and of growth factors)	Prototypic mouse M1 and M2 markers cannot be used to characterize human TAMs
	M2: Arg1, Ym1, VEGF …	M2-type: growth factors (TGF-β, VEGF, EGF, PDGF), IL-10
Polarization versus activation	Resting (M2) and LPS-stimulated (M1) cells are usually compared	Human Mφ and TAMs require to be stimulated (such as via CD40 or TLRs) to reveal their phenotypes		Human Mφ polarization and activation are two independent processes

Arg1, arginase 1; DCs, dendritic cells; EGF, epithelial growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MHC-II, major histocompatibility complex class II; Mφ, macrophage; PDGF, platelet-derived growth factor; PRR, pattern recognition receptors; TAMs, tumor-associated macrophages; TGF-β, transforming growth factor-β; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.