Neutrophil plasticity in the tumor microenvironment

Abstract

Neutrophils act as the body’s first line of defense against infection and respond to diverse inflammatory cues, including cancer. Neutrophils display plasticity, with the ability to adapt their function in different inflammatory contexts. In the tumor microenvironment, neutrophils have varied functions and have been classified using different terms, including N1/N2 neutrophils, tumor-associated neutrophils, and polymorphonuclear neutrophil myeloid–derived suppressor cells (PMN-MDSCs). These populations of neutrophils are primarily defined by their functional phenotype, because few specific cell surface markers have been identified. In this review, we will discuss neutrophil polarization and plasticity and the function of proinflammatory/anti-inflammatory and protumor/antitumor neutrophils in the tumor microenvironment. We will also discuss how neutrophils with the ability to suppress T-cell activation, referred to by some as PMN-MDSCs, fit into this paradigm.

Single-cell transcriptome profiling reveals neutrophil heterogeneity and orchestrated maturation during homeostasis and bacterial infection

“…A number of neutrophil subpopulations have previously been identified through functional and phenotypic associations in various models, including but are not limited to human CD177 + (Hu et al, 2009;Silvestre-Roig et al, 2016;Wu et al, 2016;Zhou et al, 2018), olfactomedin-4 + (OLFM4) (Clemmensen et al, 2012), TCR-expressing (Puellmann et al, 2006), CD49d + VEGFR1 high CXCR4 high angiogenic (Christoffersson et al, 2012;Massena et al, 2015), CD63 + (Tirouvanziam et al, 2008), IL-13 + (Chen et al, 2014), CD49 + (Cheung et al, 2010;Tsuda et al, 2004), IL-17producing (Taylor et al, 2014), CD62L dim /CD16 bright and CD62L bright /CD16 dim (Pillay et al, 2012), immunosuppressive CD11c bright CD62L dim CD11b bright CD16 bright (Pillay et al, 2012), CD16 dim banded (Leliefeld et al, 2018), CD62L dim (Tak et al, 2017), mature CD10 + and immature CD10 - (Marini et al, 2017), and tumor- Neutrophils are now known to be important in cancer. Two tumor-associated neutrophil (TAN) subpopulations are present in tumors: pro-inflammatory antitumorigenic N1 neutrophils and pro-tumorigenic N2 neutrophils (Fridlender et al, 2009;Giese et al, 2019;Sionov et al, 2015). N1 TANs showed a more immunostimulatory mRNA profile than N2 neutrophils, expressing higher levels of TNF-α, CCL3, iNOS, and ICAM-1.…”

γδ T cells in cancer: a small population of lymphocytes with big implications

“…34,89,93 They induced angiogenesis and the recruitment of neutrophils, generally associated with poor prognosis in cancer. 94 IL-17-producing cd T cells also promoted the recruitment of immunosuppressive neutrophils and small peritoneal macrophages, which inhibit CTL response and enhance tumor growth. Nevertheless, neutrophils display phenotypical and functional plasticity depending on the tumor microenvironment, and have been found to also contribute to antitumor immune response, notably through antibody-dependent cellular cytotoxicity (ADCC) and recruitment of other immune cells.…”

“…Nevertheless, neutrophils display phenotypical and functional plasticity depending on the tumor microenvironment, and have been found to also contribute to antitumor immune response, notably through antibody-dependent cellular cytotoxicity (ADCC) and recruitment of other immune cells. 94 IL-17-producing cd T cells also promoted the recruitment of immunosuppressive neutrophils and small peritoneal macrophages, which inhibit CTL response and enhance tumor growth. 34,88,90,93 In a model of pancreatic ductal adenocarcinoma (PDA), IL-17 + IL-10 + cd T cells were also directly suppressive of T-cell responses.…”

CyTOF reveals phenotypically-distinct human blood neutrophil populations differentially correlated with melanoma stage

“…Neutrophil heterogeneity has become an active research area, particularly with regards to cancer progression. 17 Comprehensive examination by flow cytometry has revealed that neutrophils express a complex surface antigen profile. 27 However, due to the limitations imposed by flow cytometry, researchers have had to arbitrarily select only a few surface markers to examine at a particular time.…”

“…16 Interestingly, work in this field has also suggested differential involvement of neutrophil subpopulations in cancer. 17,18 Thus, the development of neutrophil consensus markers is required for improving our understanding of neutrophil biology and its relationship to disease progression.…”