Table 3.

Characteristics of anti- and pro-tumor neutrophils. The table emphasizes some specific traits that have been attributed to the activation and function of anti- versus pro-tumor neutrophils. Concerning the heterogeneous “N2” population, some of the traits are related to the immature LDNs (labeled with *) or the senescent mature neutrophils (labeled with **). Most studies on “N2” neutrophils have not discerned between the different “N2” subpopulations, and thus the general concept is provided. The section number in which the subject is discussed is mentioned in parentheses.

	Anti-Tumor Neutrophils (“N1”)	Pro-Tumor Neutrophils (“N2”)	References
Neutrophil subpopulation (Section 3)	Mainly mature HDN with hypersegmented nuclei	LDN; G-MDSC; immature neutrophils with banded or ring-like nuclei; senescent neutrophils	[46,47,60,67,144,145]
Induction of the phenotype (Section 4.1 and Section 4.2)	CXCL2 + GM-CSF/G-CSF Diverse cytokines (e.g., CCL2, CCL3, CCL5, CXCL5, CXCL12 (SDF-1) and CXCL16) IFNβ IFNγ + TNFα IL-17 Resolvin D1	CXCL5, CXCL8, CXCL17, CCL3/4/5 fMLP, TNFα or LPS G-CSF, GM-CSF IL-1β, IL-4, IL-6, IL-11, IL-35 IL-6 + GM-CSF IL-17 + G-CSF PGE2, S100A8/S100A9, VEGF TGFβ Hyaluronan fragments MIF Oxysterol Cancer-specific peptide of Vacuolar-ATPase a2 isoform (a2NTD)	[9,14,20,53,58,60,61,62,68,71,75,77,84,116,118,159,168,169,170,171,172,173,174,175,177,178,179,180,181,182,183,184,185,186,194,200,201,202,203,207,208,209,210,211,212,213,214,215,216,217,218]
Characteristics of the subpopulations (Section 3, Section 4.3 and Section 4.4)	Increased Mac-1 and ICAM-1 expression. CD62LhighCXCR4low Produce H2O2, O2−·, OCl−, FasL and TRAIL, which are cytotoxic to tumor cells Secrete CXCL13, CCL3, CCL6, CXCL10, TNFα	CD62LhighCXCR4low * CD62LlowCXCR4highTLR4high ** Increased Mac-1 and ICAM-1 expression ** Increased PD-L1 expression * Produce H2O2, O2−·, OCl−, NO·, ONOO−·, ARG1, IDO Secrete MMP8/9, NE, CathG, VEGF, Bv8, FGF2 HGF, CCL2, CCL5, CCL17, CXCL4 LOX-1, FATP2, COX2, iNOS IL-1β, TNFα, IL-6, Oncostatin M, Transferrin NET production ** Represses the cytotoxic activity of T and NK cells *	[15,24,47,53,59,60,61,75,77,114,116,118,155,167,168,172,202,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237]
Recognition of tumor cells (Section 5)	Cathepsin G-RAGE interaction	Mac-1–ICAM-1 interaction L-selectin-sialomucin interaction PR3-RAGE interaction	[54,227,238,239,240,241,242,243,244]
Activated intracellular signaling pathways of the subpopulations (Section 3, Section 4.1 and Section 4.2)	PI3K and p38 MAPK signaling pathways Src kinase Upregulation of Rab27a	STAT3 activation JAK/STAT5β Immature LDNs possess a C/EBPε transcriptional signature	[21,53,157,158,203,245,246]