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Neutrophils in cancer: dual roles through intercellular interactions

Oncogene volume 43, pages 1163–1177 (2024)Cite this article

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Abstract

Neutrophils, the most abundant immune cells in human blood, play crucial and diverse roles in tumor development. In the tumor microenvironment (TME), cancer cells regulate the recruitment and behaviors of neutrophils, transforming some of them into a pro-tumor phenotype. Pro-tumor neutrophils interact with cancer cells in various ways to promote cancer initiation, growth, and metastasis, while anti-tumor neutrophils interact with cancer cells to induce senescence and death. Neutrophils can also interact with other cells in TME, including T cells, macrophages, stromal cells, etc. to exert anti- or pro-tumor functions. In this review, we will analyze the anti- and pro-tumor intercellular interactions mediated by neutrophils, with a focus on generalizing the mechanisms underlying the interaction of neutrophils with tumor cells and T cells. Furthermore, we will provide an overview of cancer treatment strategies targeting neutrophil-mediated cellular interactions.

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Fig. 1: The anti-tumor effects of neutrophils in TME.
Fig. 2: Developing the anti-tumor therapeutic value of neutrophils.
Fig. 3: Tumor function in orchestrating pro-tumor responses of neutrophils.
Fig. 4: Neutrophil-tumor communications facilitate tumor progression.
Fig. 5: The interactions between non-cancer cells and neutrophils promote cancer development.
Fig. 6: Therapy to inhibit neutrophil recruitment.

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Acknowledgements

This work was supported by Zhejiang University-University of Edinburgh Institute (ZJE) and Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University. We also acknowledge the help of members in JL’s lab.

Funding

This work was supported by grants to JL from the Natural Science Foundation (NSF) of China (General Grant: 82172899), the NSF of Zhejiang Province (Distinguished Young Scholars: LR22H160002), Dr. Li Dak Sum & Yip Yio Chin Development Fund for Regenerative Medicine, Zhejiang University, and Dynamic Research Enterprise for Multidisciplinary Engineering Sciences (DREMES) at Zhejiang University and the University of Illinois at Urbana-Champaign, funded by Zhejiang University.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310029, China

    Xinyu Yu, Zijin Wang, Yaping Xu & Jian Liu

  2. Edinburgh Medical School: Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK

    Xinyu Yu, Changhui Li, Zijin Wang, Yaping Xu & Jian Liu

  3. Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China

    Shiqun Shao

  4. Biomedical and Heath Translational Research Center of Zhejiang Province, Haining, China

    Fangwei Shao & Jian Liu

  5. -University of Illinois Urbana-Champaign Institute, Zhejiang University, Haining, 314400, China

    Fangwei Shao

  6. National Key Laboratory of Biobased Transportation Fuel Technology, Zhejiang University, Hangzhou, 310027, China

    Fangwei Shao

  7. Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Hua Wang

  8. Hangzhou Cancer Institution, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310002, China

    Jian Liu

  9. Cancer Center, Zhejiang University, Hangzhou, 310058, China

    Jian Liu

  10. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China

    Jian Liu

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  1. Xinyu Yu
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  2. Changhui Li
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  3. Zijin Wang
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  7. Hua Wang
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  8. Jian Liu
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Contributions

J. Liu designed, supervised and supported the whole project. X. Yu wrote the manuscript. C. Li, Y. Xu, Z. Wang, S. Shao, F. Shao, and H. Wang revised the manuscript. C. Li contributed to some figures. All authors contributed to the article and approved the submitted version.

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Correspondence to Jian Liu.

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Yu, X., Li, C., Wang, Z. et al. Neutrophils in cancer: dual roles through intercellular interactions. Oncogene 43, 1163–1177 (2024). https://doi.org/10.1038/s41388-024-03004-5

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