Tumour-associated neutrophils in patients with cancer

The role and importance of neutrophils in cancer has become increasingly apparent over the past decade. Neutrophils accumulate in the peripheral blood of patients with cancer, especially in those with advanced-stage disease, and a high circulating neutrophil-to-lymphocyte ratio is a robust biomarker of poor clinical outcome in various cancers. To date, most studies investigating the role of neutrophils in cancer have involved animal models or investigated the function of circulating human neutrophils. Thus, only limited information is available on the roles of intratumoural neutrophils (also known as tumour-associated neutrophils (TANs)) in patients with cancer. In this Review, we initially describe the evidence correlating the neutrophilto-lymphocyte ratio with prognosis, followed by a discussion on the predictive value of TANs, which remains debatable, with conflicting data from different cancer types, including variations based on neutrophil location within and/or around the tumour. We then explore available data on the implications of TAN phenotypes and functions for cancer development and progression, highlighting the reported effects of various treatments on TANs and how neutrophils might affect therapeutic efficacy. Finally, we examine the various compounds capable of modulating neutrophils and suggest future research directions that might ultimately enable the manipulation of TANs in patients with cancer.