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The Emerging Role of Neutrophils in Cancer: Molecular Aspects of Plasticity and Potential Therapeutic Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 5695

Special Issue Editor

Dr. Deepika Awasthi

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA
Interests: immunology; cell metabolism; inflammation & infection; cancer; redox biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neutrophils are the most abundant population of immune cells and perform a variety of functions, including neutrophil extracellular trap formation, phagocytosis, and the release of proteolytic enzymes, cytokines, chemokines, and immunosuppressive molecules. These functions not only serve as a defense mechanism against inflammation and infection but also regulate adaptive immunity in cancers. Recent research has highlighted the growing relevance of neutrophils in the tumor microenvironment, where they can have both pro- and anti-tumor effects, but their precise role remains unclear. Due to their rapid turnover from bone marrow and easy recruitment to metastatic sites, neutrophils can express a unique transcription signature that can render them either pro- or anti-tumorogenic. Tumor-infiltrating neutrophils induce the expression of chemokine receptors and molecules such as arginase 1 (ARG1), PDL-1, and reactive oxygen/nitrogen species (RONS). To fully understand the molecular aspects of neutrophil function in tumors, further research is necessary, with a focus on signaling pathways, gene expression profiles, and molecular interactions within the tumor microenvironment. Investigating the impact of factors such as hypoxia and inflammation on neutrophil function in tumors may also yield valuable insights. This Special Issue invites researchers to contribute their work on the intriguing molecular aspects of neutrophil plasticity as pro- and anti-metastatic immune cells in various cancers, with the potential to develop new strategies for targeting neutrophils in cancer therapy and improving patient outcomes.

Dr. Deepika Awasthi
Guest Editor

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Keywords

  • neutrophils
  • cancer
  • tumor microenvironment
  • tumor-associated neutrophils
  • innate immunity

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Published Papers (2 papers)

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15 pages, 1978 KiB  
Article
SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity
by Panagiota Bouti, Colin Blans, Bart J. A. M. Klein, Debarati Shome, Reza Nadafi, Michel Van Houdt, Karin Schornagel, Paul J. J. H. Verkuijlen, Virginie Roos, Rogier M. Reijmers, Robin Van Bruggen, Taco W. Kuijpers and Hanke L. Matlung
Int. J. Mol. Sci. 2023, 24(24), 17141; https://doi.org/10.3390/ijms242417141 - 5 Dec 2023
Cited by 1 | Viewed by 2589
Abstract
Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding [...] Read more.
Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding receptor (SIGLEC) family. Here, we demonstrate that interaction between tumor cell-expressed sialic acids and SIGLEC-5/14 on neutrophils inhibits antibody-dependent cellular cytotoxicity (ADCC). We observed that conjugate formation and trogocytosis, both essential processes for neutrophil ADCC, were limited by the sialic acid-SIGLEC-5/14 interaction. During neutrophil-tumor cell conjugate formation, we found that inhibition of the interaction between tumor-expressed sialic acids and SIGLEC-5/14 on neutrophils increased the CD11b/CD18 high affinity conformation. By dynamic acoustic force measurement, the binding between tumor cells and neutrophils was assessed. The interaction between SIGLEC-5/14 and the sialic acids was shown to inhibit the CD11b/CD18-regulated binding between neutrophils and antibody-opsonized tumor cells. Moreover, the interaction between sialic acids and SIGLEC-5/14-consequently hindered trogocytosis and tumor cell killing. In summary, our results provide evidence that the sialic acid-SIGLEC-5/14 interaction is an additional target for innate checkpoint blockade in the tumor microenvironment. Full article
(This article belongs to the Special Issue The Emerging Role of Neutrophils in Cancer: Molecular Aspects of Plasticity and Potential Therapeutic Targets)
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Review

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22 pages, 977 KiB  
Review
Neutrophils at the Crossroads: Unraveling the Multifaceted Role in the Tumor Microenvironment
by Deepika Awasthi and Aditya Sarode
Int. J. Mol. Sci. 2024, 25(5), 2929; https://doi.org/10.3390/ijms25052929 - 2 Mar 2024
Cited by 4 | Viewed by 2307
Abstract
Over the past decade, research has prominently established neutrophils as key contributors to the intricate landscape of tumor immune biology. As polymorphonuclear granulocytes within the innate immune system, neutrophils play a pivotal and abundant role, constituting approximately ∼70% of all peripheral leukocytes in [...] Read more.
Over the past decade, research has prominently established neutrophils as key contributors to the intricate landscape of tumor immune biology. As polymorphonuclear granulocytes within the innate immune system, neutrophils play a pivotal and abundant role, constituting approximately ∼70% of all peripheral leukocytes in humans and ∼10–20% in mice. This substantial presence positions them as the frontline defense against potential threats. Equipped with a diverse array of mechanisms, including reactive oxygen species (ROS) generation, degranulation, phagocytosis, and the formation of neutrophil extracellular traps (NETs), neutrophils undeniably serve as indispensable components of the innate immune system. While these innate functions enable neutrophils to interact with adaptive immune cells such as T, B, and NK cells, influencing their functions, they also engage in dynamic interactions with rapidly dividing tumor cells. Consequently, neutrophils are emerging as crucial regulators in both pro- and anti-tumor immunity. This comprehensive review delves into recent research to illuminate the multifaceted roles of neutrophils. It explores their diverse functions within the tumor microenvironment, shedding light on their heterogeneity and their impact on tumor recruitment, progression, and modulation. Additionally, the review underscores their potential anti-tumoral capabilities. Finally, it provides valuable insights into clinical therapies targeting neutrophils, presenting a promising approach to leveraging innate immunity for enhanced cancer treatment. Full article
(This article belongs to the Special Issue The Emerging Role of Neutrophils in Cancer: Molecular Aspects of Plasticity and Potential Therapeutic Targets)
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