The role of neutrophils in cancer

Abstract

Introduction: It has been known for some time that neutrophils are present in the tumour microenvironment, but only recently have their roles been explored.

Sources of data: Comprehensive literature search of neutrophils and cancer (PubMed, Google Scholar and CrossRef) for key articles (systematic reviews, meta-analyses, primary research). References from these articles cross-checked for additional relevant studies.

Areas of agreement: Neutrophils are a heterogeneous population with both pro- and antitumour roles, and display plasticity. Several neutrophil subpopulations have been identified, defined by a combination of features (density, maturity, surface markers, morphology and anatomical site).

Areas of controversy: Limitations in translating murine tumour models to human pathology and paucity of human data. Consensus in defining human neutrophil subpopulations.

Growing points: Neutrophils as therapeutic targets and as possible playmakers in the biological response to newer targeted cancer drugs.

Areas timely for developing research: Understanding the metabolic programming of neutrophils in the tumour microenvironment.

Fig. 1

Neutrophil subpopulations defined by density, maturity, surface markers, morphology and anatomical site. At present, it is unclear whether there is any crossover between LDN, N2 TAN and G-MDSC populations. LDN, low-density neutrophils; NDN, normal (high)-density neutrophils; TAN, tumour-associated neutrophils; G-MDSCs, granulocytic myeloid-derived suppressor cells.

Fig. 2

Mechanisms through which neutrophil subpopulations aid or abate tumourigenesis. The proportion of pro- and antitumour neutrophils at any one time is influx, with a degree of plasticity and a spectrum of activity. However, for cancers to progress this balance must begin to favour immature pro-tumour neutrophils.