Neutrophil phenotypes and functions in cancer: A consensus statement

Abstract

Neutrophils are the first responders to infection and inflammation and are thus a critical component of innate immune defense. Understanding the behavior of neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile and infectious diseases; however, the field of neutrophils in cancer is comparatively young. Here, we summarize key concepts and current knowledge gaps related to the diverse roles of neutrophils throughout cancer progression. We discuss sources of neutrophil heterogeneity in cancer and provide recommendations on nomenclature for neutrophil states that are distinct in maturation and activation. We address discrepancies in the literature that highlight a need for technical standards that ought to be considered between laboratories. Finally, we review emerging questions in neutrophil biology and innate immunity in cancer. Overall, we emphasize that neutrophils are a more diverse population than previously appreciated and that their role in cancer may present novel unexplored opportunities to treat cancer.

The novel compensatory reciprocal interplay between neutrophils and monocytes drives cancer progression

“…Functional investigation of neutrophil in GBM, or in cancer in general, is a nascent field (Quail et al, 2022). It has been shown at the onset of GBM formation, neutrophils have an anti-tumoral effect, but adopt a tumor-supportive phenotype as tumor progression occurs (Magod et al, 2021).…”

“…Monocytes are a minority in blood circulation, yet they give rise to the dominant infiltrates in GBM; whereas neutrophils, the most abundant in the blood, rarely invade GBM (except for MES tumors in both human and mice)? It is speculated that Tp53 loss, either alone or in combination with Kras or Pten , create microenvironments that preferentially favor neutrophil infiltration in various solid tumors (Quail et al, 2022). However, Tp53 mutation occurs at a very high prevalence across many cancer types, ranging from 30% to 47% in brain, liver, lung, skin, ovarian and many other cancers (Olivier et al, 2010).…”

Neutrophil proteomics identifies temporal changes and hallmarks of delayed recovery in COVID19

“…A hallmark of severe disease is T-cell lymphopenia in combination with increased blood neutrophil counts (2,(14)(15)(16) . Neutrophils are key effector cells of the innate immune response that play a role in responses to pathogens and tumours (17,18) and in severe COVID19 there is evidence of emergency myelopoiesis and the appearance of circulating immature and dysfunctional neutrophils in peripheral blood (11,(19)(20)(21)(22) . There is also a signature of neutrophil activation in patients with severe COVID19 that predicts disease trajectory (23,24) , as well as evidence of increased NETosis (25) .…”

ETV4 mediated tumor-associated neutrophil recruitment promotes lymphangiogenesis and lymphatic metastasis of bladder cancer

“…TANs express abundant chemokine receptors CXCR1 and CXCR2, which are important for their recruitment to TME, where chemokines (such as CXCL1, CXCL2, CXCL5, CXCL6 and CXCL8) are secreted by cancer cells and in ltrated immune cells 19 . TANs may exhibit an anti-tumor effect by releasing TSP-1, elastase, tumor necrosis factor (TNF), nitric oxide (NO) and reactive oxygen species (ROS), but more frequently exert a pro-tumor effect by promoting immunosuppression, tumor cell proliferation, genetic instability, angiogenesis and metastasis [20][21][22][23][24] . In addition to angiogenesis, accumulated neutrophils also contribute to lymphangiogenesis via regulating VEGFA bioactivity at sites of in ammation 25 .…”