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Neutrophils in cancer: heterogeneous and multifaceted

Nature Reviews Immunology volume 22, pages 173–187 (2022)Cite this article

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Abstract

Neutrophils are the most abundant myeloid cells in human blood and are emerging as important regulators of cancer. However, their functional importance has often been overlooked on the basis that they are short-lived, terminally differentiated and non-proliferative. Recent studies of their prominent roles in cancer have led to a paradigm shift in our appreciation of neutrophil functional diversity. This Review describes how neutrophil diversification, which in some contexts can lead to opposing functions, is generated within the tumour microenvironment as well as systemically. We compare neutrophil heterogeneity in cancer and in other pathophysiological contexts to provide an updated overview of our current knowledge of the functions of neutrophils in cancer.

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Fig. 1: Neutrophil development in the bone marrow.
Fig. 2: Neutrophil effects on tumour initiation and growth.
Fig. 3: Neutrophil perturbations during metastatic progression.
Fig. 4: Neutrophil engagements during metastatic progression.

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Acknowledgements

The authors thank D. Araujo (La Jolla Institute for Immunology (LJI)) for helpful edits, E. Nolan (The Francis Crick Institute) for critically reading the manuscript and H. Q. Dinh (University of Wisconsin-Madison) and M. A. Meyer (LJI) for helpful discussion of neutrophil developmental trajectories. This work was supported in part by the US National Institutes for Health (P01HL152958, P01HL136275 and U01CA224766 to C.C.H.), and by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001112), the UK Medical Research Council (FC001112) and the Wellcome Trust (FC001112), and by a European Research Council grant (CoG-H2020-725492 to I.M).

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  1. Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA, USA

    Catherine C. Hedrick

  2. Tumour–Host Interaction Laboratory, The Francis Crick Institute, London, UK

    Ilaria Malanchi

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Nature Reviews Immunology thanks Z. Fridlender, A. Hidalgo and other anonymous reviewers for their contribution to the peer review of this work.

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Hedrick, C.C., Malanchi, I. Neutrophils in cancer: heterogeneous and multifaceted. Nat Rev Immunol 22, 173–187 (2022). https://doi.org/10.1038/s41577-021-00571-6

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