Figure 4.

Neutrophil Populations in Cancer.

Humans: suppressive low-density neutrophils (LDNs)/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) (Box 1) are the main neutrophil subpopulations in the blood of cancer patients 57., 66., 124.. However, in some studies LDNs have been defined as PMN-MDSCs without testing their inhibitory actions on T cell functions, or have not even been reported to be suppressive 54., 109.. Furthermore, whether and to what degree circulating normal-density neutrophils (NDNs) from cancer patients also display suppressive properties remains poorly defined. Depending on the study, human tumor-associated neutrophils (TANs) have been reported to either promote 64., 119. or inhibit 120., 121. T cell functions. A population of human leukocyte antigen DR isotype (HLA-DR)⁺ antigen-presenting cell (APC)-like hybrid TANs supporting antitumoral T cell responses has been isolated from the tumor tissue of early-stage lung cancer patients [64]. Mice: populations of immature neutrophils displaying immunosuppressive properties have been reported in the blood (LDNs/PMN-MDSCs), spleen, bone marrow (BM) and tumor tissue of tumor-bearing mice (Box 2) 57., 66.. In addition, two subtypes of mature circulating neutrophils have been proposed to be present in tumor-bearing mice, namely NDNs (displaying antitumor properties) and LDNs (displaying immunosuppressive and protumor properties) [122]. Similarly, N1 TANs displaying antitumor properties (e.g., promotion of antitumor T cell responses and direct tumor cytotoxicity) or N2 TANs (both mature and immature cells) displaying protumor properties (e.g., immunosuppression, promotion of tumor cell proliferation/survival, promotion of angiogenesis and tumor cell extravasation into distant metastatic tissue) have also been reported within tumor tissues [109].