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  • Review Article
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Tumour-associated neutrophils in patients with cancer

Abstract

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 neutrophil-to-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.

Key points

  • The traditionally held belief that neutrophils are merely a bystander in the tumour microenvironment has been revolutionized over the past decade, and research has now established that neutrophils have an important contribution in the initiation, development and progression of cancer.

  • Tumour-associated neutrophils (TANs) predict poor overall survival in many types of cancer, with their location in the tumour and specific markers being important deferential determinants.

  • Data on the phenotype and function of TANs in patients with cancer remain limited and are mostly from those with early stage disease.

  • Both antitumour and protumour functions of TANs have been described in patients with cancer, with both direct and indirect effects on tumour cells as well as indirect effects on the tumour microenvironment and its immune content.

  • The importance of neutrophils in mediating the effects of existing and established cancer therapies is an emerging and exciting area of research.

  • The ability to target TANs clinically, either by suppression or phenotypic manipulation, might be an important outcome of research into the role of TANs in cancer and could enable the development of a new generation of immunotherapies.

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Fig. 1: Prognostic implications of neutrophils and their location in patients with cancer.
Fig. 2: Proposed phenotypes, markers and functions of tumour-associated neutrophils in a range of human cancers.
Fig. 3: Mechanisms by which routinely used treatments of cancer might modulate the phenotype and/or functions of cancer-related neutrophils.

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Acknowledgements

The authors’ research is supported by the Israel Society Foundation and the Israel Cancer Research Foundation.

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Shaul, M.E., Fridlender, Z.G. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol 16, 601–620 (2019). https://doi.org/10.1038/s41571-019-0222-4

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