Neutrophil phenotypes and functions in cancer: A consensus statement

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,...

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Published inThe Journal of experimental medicine Vol. 219; no. 6
Main Authors Quail, Daniela F., Amulic, Borko, Aziz, Monowar, Barnes, Betsy J., Eruslanov, Evgeniy, Fridlender, Zvi G., Goodridge, Helen S., Granot, Zvi, Hidalgo, Andrés, Huttenlocher, Anna, Kaplan, Mariana J., Malanchi, Ilaria, Merghoub, Taha, Meylan, Etienne, Mittal, Vivek, Pittet, Mikael J., Rubio-Ponce, Andrea, Udalova, Irina A., van den Berg, Timo K., Wagner, Denisa D., Wang, Ping, Zychlinsky, Arturo, de Visser, Karin E., Egeblad, Mikala, Kubes, Paul
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 06.06.2022
SeriesCancer Focus
Subjects
Cancer Focus
Humans
Immunity, Innate
Inflammation
Innate immunity and inflammation
Neoplasms - genetics
Neutrophils
Phenotype
Review
Tumor immunology
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Summary: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.
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T.K. van den Berg’s present address is Byondis BV, Nijmegen, Netherlands.
Disclosures: E. Eruslanov reported a patent to the use of HLA-DR+CD32hiCD64hi hybrid neutrophils with characteristics of antigen-presenting cells to augment therapy for cancer or infectious diseases pending. Z.G. Fridlender reported “other” from Immunyx outside the submitted work; in addition, Z.G. Fridlender had a patent to ID - 6494-1 licensed "Immunyx." Z. Granot reported personal fees from Immunyx Pharma outside the submitted work. A. Hidalgo is a paid consultant for Flagship Pioneering, which is not related to this work. M.J. Pittet reported personal fees from AstraZeneca, Debiopharm, Elstar Therapeutics, ImmuneOncia, KSQ Therapeutics, MaxiVax, Merck, Molecular Partners, Third Rock Ventures, and Tidal outside the submitted work; in addition, M.J. Pittet has been a consultant for Aileron Therapeutics, Cygnal Therapeutics, and Siamab Therapeutics. T.K van den Berg is an inventor on patent application WO2009/131453 A1, owned by Sanquin Blood Supply Organization, licensed to Byondis BV, related to the targeting of CD47-SIRPα in cancer. D.D. Wagner reported personal fees from Takeda Pharmaceutical and “other” from Neutrolis, SAB during the conduct of the study. K.E. de Visser reported grants from Roche/Genentech and personal fees from Macomics outside the submitted work. M. Egeblad is a member of the research advisory board for brensocatib for Insmed, Inc, a member of the scientific advisory board for Vividion Therapeutics, Inc., and a consultant for Protalix, Inc outside the submitted work. T. Merghoub is a co-founder and holds equity in IMVAQ Therapeutics. He is a consultant of Immunos Therapeutics, ImmunoGenesis, and Pfizer. In addition, T Merghoub has research support from Bristol-Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals Inc., Peregrine Pharmaceuticals Inc., Adaptive Biotechnologies, Leap Therapeutics Inc., and Aprea. He has patents on applications related to work on oncolytic viral therapy, α-virus-based vaccine, neo antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4. No other disclosures were reported.
ISSN:0022-1007
1540-9538
1540-9538
DOI:10.1084/jem.20220011