Granulocyte-colony stimulating factor: Missing link for stratification of type 2–high and type 2–low chronic rhinosinusitis patients

Nevel, Sharon Van; Declercq, Jozefien; Holtappels, Gabriële; Lambrecht, Bart; Bachert, Claus

doi:10.1016/j.jaci.2022.02.019

Cited by 12 publications

(10 citation statements)

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“…In Asian patients, both numbers of neutrophils and rates of apoptosis correlated with G-CSF in nasal polyps and suppressed apoptosis could be reversed by anti-G-CSF treatment [25]. These observations were recently confirmed in Caucasian patients with low-type 2 CRSwNP [26 ▪ ]. It has been shown that co-stimulation of neutrophils with GM-CSF, TNF-α and IL-4 leads to the generation of long-living populations of neutrophils; and the concentration of all these mediators have been reported to be increased in CRS mucosa [27,28].…”

Section: Neutrophil Infiltration and Survival In Chronic Rhinosinusitismentioning

confidence: 63%

“…As the type 2 CRSsNP patients have worse clinical outcomes by means of recurrence, comorbid asthma and reduced smell/taste, neutrophils cannot be associated with a more severe clinical outcome in CRSsNP. Interestingly, more and more studies over the last decade report the existence of a mixed eosinophilic-neutrophilic inflammation, associated with high type 2 responses and a worse clinical outcome in about 26…”

Section: Introductionmentioning

confidence: 99%

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Neutrophilic inflammation in chronic rhinosinusitis

Delemarre

Bachert

2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewOver the last years, extensive research has been done on neutrophils and their contribution in chronic rhinosinusitis (CRS), and made it clear that they are more than just a bystander in this disease. In this article, we will review all recent publications on this topic and look to what the future hold regarding therapeutics targeting the neutrophilic inflammation in CRS. Recent findingsEvidence is growing that the presence of neutrophils are associated with a worse disease outcome in certain CRS patient groups. They are highly activated in type 2 inflammations and exhibit damaging properties through their proteases, contributing to the chronicity of the disease. Several recent studies identified useful biomarkers and targets for future therapeutics.

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Section: Neutrophil Infiltration and Survival In Chronic Rhinosinusitismentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Neutrophilic inflammation in chronic rhinosinusitis

Delemarre

Bachert

2022

Current Opinion in Allergy &Amp; Clinical Immunology

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“…Although upregulation of neutrophil infiltration was found in Chinese patients with both eosinophilic and noneosinophilic CRSwNP, noneosinophilic CRSwNP Chinese patients displayed even higher numbers of neutrophils than eosinophilic CRSwNP patients 61–63 . Recently, Nevel et al also found that T2‐low CRSwNP patients have elevated levels of neutrophils compared to T2‐high CRSwNP patients in Western countries 66 . Recently, Wang et al found that IL‐36γ produced by nasal epithelial cells could activate neutrophils and further exaggerate neutrophilic inflammation by promoting the production of neutrophil chemokines in CRS 63 .…”

Section: Cellular Traitsmentioning

confidence: 98%

“…63 By performing a comprehensive and integrated analysis of neutrophilic inflammation in a large cohort of CRSwNP patients in China, Ruan et al identified granulocyte-colony stimulating factor (G-CSF) as an important factor in suppressing neutrophil apoptosis and promoting tissue neutrophilia in Chinese CRSwNP patients, 67 which was confirmed in White CRSwNP patients. 66 Interestingly, although IL-17 has been demonstrated to promote neutrophilic inflammation in infectious and autoimmune diseases, there was a weak or no correlation between IL-17A and neutrophil levels in CRS in both Chinese and Western CRSwNP patients, disfavouring a role of IL-17A in the development of neutrophilic inflammation in CRSwNP. 6 Neutrophilic inflammation is also associated with poor treatment outcomes in CRS patients.…”

Section: Non-eosinophilic Inflammationmentioning

confidence: 98%

“…[61][62][63] Recently, Nevel et al also found that T2-low CRSwNP patients have elevated levels of neutrophils compared to T2-high CRSwNP patients in Western countries. 66 Recently, Wang et al found that IL-36γ produced by nasal epithelial cells could activate neutrophils and further exaggerate neutrophilic inflammation by promoting the production of neutrophil chemokines in CRS. 63 By performing a comprehensive and integrated analysis of neutrophilic inflammation in a large cohort of CRSwNP patients in China, Ruan et al identified granulocyte-colony stimulating factor (G-CSF) as an important factor in suppressing neutrophil apoptosis and promoting tissue neutrophilia in Chinese CRSwNP patients, 67 which was confirmed in White CRSwNP patients.…”

Section: Non-eosinophilic Inflammationmentioning

confidence: 99%

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Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review

Yao

Zhu

Zeng

et al. 2022

Clinical Otolaryngology

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Objectives: To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia.Design: This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. Results and Conclusion: CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.

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Prolonged Survival of Neutrophils Induced by Tumor‐Derived G‐CSF/GM‐CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma

Zhu,

Heng,

et al. 2024

Advanced Science

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Tumor‐associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor‐derived G‐CSF and GM‐CSF through the activation of the PI3K‐AKT signaling pathway, upregulation of anti‐apoptotic Mcl‐1 expression, and downregulation of activated Caspase‐3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G‐CSF and GM‐CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.

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Granulocyte-colony stimulating factor: Missing link for stratification of type 2–high and type 2–low chronic rhinosinusitis patients

Cited by 12 publications

References 50 publications

Neutrophilic inflammation in chronic rhinosinusitis

Neutrophilic inflammation in chronic rhinosinusitis

Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review

Prolonged Survival of Neutrophils Induced by Tumor‐Derived G‐CSF/GM‐CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma

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