Tumour macrophages as potential targets of bisphosphonates

Table 1 Difference between M1, M2 and TAM activation, membrane receptors, cytokines/chemokines produced and markers.

	M1-Classically Activated	M2-Alternatively Activated	TAMS	References
Activation	INFγ, LPS	IL-4, IL-13, IL-10	CSF-1, VEGF, CCL2, CCL3, CCL4, CCL5, CCL8, MCP-1, IL-4, IL-13, IL-10, TGFβ-1, PGE₂.	Coffelt et al [4] Joyce and Pollard [9] Mantovani et al [84]
Membrane Receptors	TLR2, TLR4, CD16,CD32, CD64, CD80, CD86	Scavenger receptor A, Scavenger receptor B, CD14, CD23, CD163	CD11b⁺, CD14^-, CD31^-, CD45⁺, CD68⁺, CD117^-, CD122^-, CD146^-, CD204⁺, CD206⁺, CCR2⁺,CSF1R⁺, MHCII⁺, CD23⁺, CD163⁺, CXCR4⁺, VEGFR1⁺, VEGFR2^-, F4/80⁺(mice)	[4, 9, 84]
Cytokines produced	IL-1, IL-6, IL-12, TNF, RNI, ROI	IL-1ra, IL-1 decoy receptor, EGF, FGF, VEGF, TNF-β,	bFGF, FGF, HFG, EGFR, PDGF, VEGF, ANG1, ANG2, IL-1, IL-8, TNF-α, TP, MMP-2, MMP-2, MMP-9, NO, CSF-1	[4, 9, 84]
Chemokines produced	CCL-2, CCL-3, CCL-4, CCL-5 CXCL8, CXCL9, CXCL10, CXCL11	CCL-12, CCL-16, CCL-17, CCL-18, CCL-22, CCL-24	CCL-2, CCL-3	[4, 9, 84]
Marker	iNOS	Arginase	F4/80 (mice), CD34 (humans)	[4, 9, 84]

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