B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer

Pylaeva, Ekaterina; Ozel, Irem; Squire, Anthony; Spyra, Ilona; Wallner, Charlotte; Korek, Magdalena; Korschunow, Georg; Domnich, Maksim; Siakaeva, Elena; Goetz, Moritz; Bànkfalvi, Àgnes; Lang, Stephan; Kansy, Benjamin; Jabłońska, Jadwiga

doi:10.3390/cancers13123092

Cited by 6 publications

(6 citation statements)

References 39 publications

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“…The increased expression of MHC class II on LN neutrophils in healthy organ donors was also demonstrated (Lok et al, 2019). Recently, we could also demonstrate the association between the infiltration of LNs by activated neutrophils and B cell responses in patients with HNC (Pylaeva et al, 2021). In animal models, co-culture of murine LN neutrophils stimulated with OVA-containing immune complexes and OVA-specific OT-II CD4 T cells resulted in increased expression of CD25 and CD69, early markers of T cell activation (Lok et al, 2019).…”

Section: Discussionmentioning

confidence: 63%

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Pylaeva¹,

Korschunow²,

Spyra³

et al. 2022

Cell Reports

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Section: Discussionmentioning

confidence: 63%

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Pylaeva¹,

Korschunow²,

Spyra³

et al. 2022

Cell Reports

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“…In many cancer entities, including head and neck cancer (HNC), high intra-tumoral neutrophil counts have been shown to be associated with a worse patient prognosis (4)(5)(6). Several responsible mechanisms have been identified, including the support of angiogenesis (7,8), the promotion of metastatic spread (9)(10)(11)(12), the regulation of B cell activation (13,14), as well as the regulation of T-cell responses in tumor tissue (15)(16)(17). Neutrophil tumorigenicity is regulated by tumor-derived factors, such as type I interferons (IFNs) (2,8,18,19), transforming growth factor beta (TGFb) (20), or granulocyte-colonystimulating factor (G-CSF) (21).…”

Section: Introductionmentioning

confidence: 99%

IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes

et al. 2022

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Tumor-draining lymph nodes (TDLNs) are the first organs where the metastatic spread of different types of cancer, including head and neck cancer (HNC), occurs and have therefore high prognostic relevance. Moreover, first anti-cancer immune responses have been shown to be initiated in such LNs via tumor-educated myeloid cells. Among myeloid cells present in TDLNs, neutrophils represent a valuable population and considerably participate in the activation of effector lymphocytes there. Tumor-supportive or tumor-inhibiting activity of neutrophils strongly depends on the surrounding microenvironment. Thus, type I interferon (IFN) availability has been shown to prime anti-tumor activity of these cells. In accordance, mice deficient in type I IFNs show elevated tumor growth and metastatic spread, accompanied by the pro-tumoral neutrophil bias. To reveal the mechanism responsible for this phenomenon, we have studied here the influence of defective type I IFN signaling on the immunoregulatory activity of neutrophils in TDLNs. Live imaging of such LNs was performed using two-photon microscopy in a transplantable murine HNC model. CatchupIVM-red and Ifnar1-/- (type I IFN receptor- deficient) CatchupIVM-red mice were used to visualize neutrophils and to assess their interaction with T-cells in vivo. We have evaluated spatiotemporal patterns of neutrophil/T-cell interactions in LNs in the context of type I interferon receptor (IFNAR1) availability in tumor-free and tumor-bearing animals. Moreover, phenotypic and functional analyses were performed to further characterize the mechanisms regulating neutrophil immunoregulatory capacity. We demonstrated that inactive IFNAR1 leads to elevated accumulation of neutrophils in TDLNs. However, these neutrophils show significantly impaired capacity to interact with and to stimulate T-cells. As a result, a significant reduction of contacts between neutrophils and T lymphocytes is observed, with further impairment of T-cell proliferation and activation. This possibly contributes to the enhanced tumor growth in Ifnar1-/- mice. In agreement with this, IFNAR1-independent activation of downstream IFN signaling using IFN-λ improved the immunostimulatory capacity of neutrophils in TDLNs and contributed to the suppression of tumor growth. Our results suggest that functional type I IFN signaling is essential for neutrophil immunostimulatory capacity and that stimulation of this signaling may provide a therapeutic opportunity in head and neck cancer patients.

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“…The activation-induced cytidine deaminase (AICDA) is an essential enzyme of the adaptive immune system. A recent study found that elevated expression of AICDA regulates the function of B cells in regional lymph nodes and significantly improves prognosis of HNSCC patients (Pylaeva et al, 2021). Tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family, has emerged as both a promising biomarker and a target for anticancer therapies (Borcherding et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

8-Gene signature related to CD8+ T cell infiltration by integrating single-cell and bulk RNA-sequencing in head and neck squamous cell carcinoma

Zhang

Zhang²,

Zhang³

2022

Front. Genet.

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Background: CD8+ T cells, a critical component of the tumor immune microenvironment, have become a key target of cancer immunotherapy. Considering the deficiency of robust biomarkers for head and neck squamous cell carcinoma (HNSCC), this study aimed at establishing a molecular signature associated with CD8+T cells infiltration.Methods: Single-cell RNA sequencing data retrieved from the Gene Expression Omnibus (GEO) database was analyzed to obtain the different cell types. Next, the cell proportions were investigated through deconvolution of RNA sequencing in the Cancer Genome Atlas (TCGA) database, and then the immune-related genes (IRGs) were identified by weighted gene co-expression network analysis (WGCNA). LASSO-Cox analysis was employed to establish a gene signature, followed by validation using a GEO dataset. Finally, the molecular and immunological properties, and drug responses between two subgroups were explored by applying “CIBERSORT”, “ESTIMATE”, and single sample gene set enrichment analysis (ssGSEA) methods.Results: A total of 215 differentially expressed IRGs were identified, of which 45 were associated with the overall survival of HNSCC. A risk model was then established based on eight genes, including DEFB1, AICDA, TYK2, CCR7, SCARB1, ULBP2, STC2, and LGR5. The low-risk group presented higher infiltration of memory activated CD4+ T cells, CD8+ T cells, and plasma cells, as well as a higher immune score, suggesting that they could benefit more from immunotherapy. On the other hand, the high-risk group showed higher abundance of activated mast cells and M2 macrophages, as well as a lower immune score.Conclusion: It was evident that the 8-gene signature could accurately predict HNSCC prognosis and thus it may serve as an index for clinical treatment.

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B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer

Cited by 6 publications

References 39 publications

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes

8-Gene signature related to CD8+ T cell infiltration by integrating single-cell and bulk RNA-sequencing in head and neck squamous cell carcinoma

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