. 2022 Dec 13;23(24):15827. doi: 10.3390/ijms232415827

Table 1.

Diverse neutrophil subpopulations in cancer in comparison with mature neutrophils in healthy individuals.

Neutrophil Type	Markers		Origin	Maturity	Location/ Detection	Life Span/ Turnover	ROS Production	Angiogenic Properties	NETosis	Interactions with Adaptive Immunity	Other Features
Neutrophil Type	Human	Murine	Origin	Maturity	Location/ Detection	Life Span/ Turnover	ROS Production	Angiogenic Properties	NETosis	Interactions with Adaptive Immunity	Other Features
Mature neutrophils	CD11b⁺ CD16⁺ CD15⁺ CD14⁻ [35,36]	CD11b⁺ Ly6G⁺ Ly6C⁻ [35,36]	Hematopoietic stem cells in bone marrow [3]	In the final steps of granulopoiesis, neutrophils gain morphological and surface markers of maturity [3]	Bone marrow, peripheral blood, spleen, and tissues [37]	In blood, neutrophils have half-lives of 12.5 h for mice and 90 h for humans [38]; in tissues, neutrophils undergo apoptosis or reverse migration [35]	At the site of infection, neutrophils release large amounts of ROS as an antimicrobial mechanism [39]	Neutrophils in tissues may exhibit a non-immune angiogenic phenotype [6]	Undergo NETosis in response to various microorganisms and endogenous stimuli [40]	Are involved in complex interactions, including the activation and regulation of other immune cells [41]	N.D.
N1 TANs	Carry markers similar to mature neutrophils		Can come from both LDNs and, most likely, NDNs in the blood and tumor microenvironment [42]	Mature cells [14]	Intratumoral [14]	N.D. Polarization to N1 by IFNs could delay neutrophil apoptosis [43,44]	Able to produce high levels of ROS [45]	IFN-β maintains the low levels of expression of angiogenic factors in N1 TANs [24]	Polarization to N1 by IFNs could ensure the capacity of N1 TANs to produce NETs [46]	Activate CD8⁺ T cells [14]; participate in antigen presentation [28]	Hyper-segmented nucleus [14]
N2 TANs	Carry markers similar to mature neutrophils		Can come from both NDNs and, most likely, LDNs [42]	Show morphological signs of immaturity [14,27]	Intratumoral [14]	N.D. Could have a prolonged life span [29]	Reduced [29]	Produce high levels of CXCR4, VEGF, and MMP9 [24]	Reduced [27]	Could recruit Tregs [28]; produce high levels of arginase [14]	Circular nucleus [14,27]
LDN	CD11b⁺ CD16⁺ CD15⁺ CD66⁺ Siglec8^- CD36^high CD61^high CD41^high Lox1^high CD226^high CD10 ^+/− [47]	CD11b⁺ Ly6G⁺ [15]	Could originate from NDNs under the action of tumor-derived factors [42]	Consist of both mature and immature populations [15]	Blood of cancer patients and tumor-bearing mice [15], could infiltrate tumors [42]	LDNs showed a lower rate of apoptosis in vitro in comparison to NDNs [15]	Increased [42]	N.D.	Immature LDNs in response to stimulation in vitro show increased ability to NETosis [48]	Express higher levels of PD-L1 in comparison to NDNs [49]	Lower phagocytic activity [42]; immature LDNs have greater bioenergetic capacity [48]
g-MDSC	CD11b⁺ CD15⁺ CD14⁻ CD66b⁺ CD33+ HLA-DR^- Lox1⁺ [19,50]	CD11b⁺ Ly6G⁺ Ly6C^low [50]	Granulocytic precursors [51]	Immature cells [35]	Bone marrow, blood, spleen, and tumors of tumor-bearing mice; blood and tumor environment of cancer patients [52]	N.D. Their turnover could be regulated by the Fas-FasL pathway [53]	Increased [54]	Could participate in tumor angiogenesis [55]	Could produce NETs under specific conditions [56]	Suppress T cells [57]	Lower density [58]; lower phagocytic activity [59]