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

Pylaeva, Ekaterina; Korschunow, Georg; Spyra, Ilona; Bordbari, Sharareh; Siakaeva, Elena; Ozel, Irem; Domnich, Maksim; Squire, Anthony; Hasenberg, Anja; Thangavelu, Kruthika; Hussain, Timon; Goetz, Moritz; Lang, Karl S.; Gunzer, Matthias; Hansen, Wiebke; Buer, Jan; Bànkfalvi, Àgnes; Lang, Stephan; Jabłońska, Jadwiga

doi:10.1016/j.celrep.2022.111171

Cited by 47 publications

(39 citation statements)

References 55 publications

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“…And it was supported by the latest evidence in HNC that neutrophils promote anti-tumour immunity by sampling tumour antigens in PT and presenting them to T cells through migration to LNs. 68 Going further, five phenotypically and functionally heterogeneous neutrophil subsets were identified in positive TDLN. And several distinct points are noteworthy.…”

Section: Discussionmentioning

confidence: 97%

Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil

Peng

Xiao-yue

Liu

et al. 2023

Clinical & Translational Med

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Background The cellular dynamics in the tumour microenvironment (TME) along with non‐small cell lung cancer (NSCLC) progression remain unclear. Methods Multiplex immunofluorescence test detecting 10 immune‐related markers on 553 primary tumour (PT) samples of NSCLC was conducted and spatial information in TME was assessed by the StarDist depth learning model. The single‐cell transcriptomic atlas of PT (n = 4) and paired tumour‐draining lymph nodes (TDLNs) (n = 5 for tumour‐invaded, n = 3 for tumour‐free) microenvironment was profiled. Various bioinformatics analyses based on Gene Expression Omnibus, TCGA and Array‐Express databases were also used to validate the discoveries. Results Spatial distances of CD4+ T cells–CD38+ T cells, CD4+ T cells–neutrophils and CD38+ T cells–neutrophils prolonged and they were replaced by CD163+ macrophages in PT along with tumour progression. Neutrophils showed unique stage and location‐dependent prognostic effects. A high abundance of stromal neutrophils improved disease‐free survival in the early‐stage, whereas high intratumoural neutrophil infiltrates predicted poor prognosis in the mid‐to‐late‐stage. Significant molecular and functional reprogramming in PT and TDLN microenvironments was observed. Diverse interaction networks mediated by neutrophils were found between positive and negative TDLNs. Five phenotypically and functionally heterogeneous subtypes of tumour‐associated neutrophil (TAN) were further identified by pseudotime analysis, including TAN‐0 with antigen‐presenting function, TAN‐1 with strong expression of interferon (IFN)‐stimulated genes, the pro‐tumour TAN‐2 subcluster, the classical subset (TAN‐3) and the pro‐inflammatory subtype (TAN‐4). Loss of IFN‐stimulated signature and growing angiogenesis activity were discovered along the transitional trajectory. Eventually, a robust six neutrophil differentiation relevant genes‐based model was established, showing that low‐risk patients had longer overall survival time and may respond better to immunotherapy. Conclusions The cellular composition, spatial location, molecular and functional changes in PT and TDLN microenvironments along with NSCLC progression were deciphered, highlighting the immunoregulatory roles and evolutionary heterogeneity of TANs.

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Section: Discussionmentioning

confidence: 97%

Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil

Peng

Xiao-yue

Liu

et al. 2023

Clinical & Translational Med

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“…Notably, FcγR-mediated endocytosis of antibody-antigen complexes converts neutrophils into a more potent APC-like cells ( 176 ) ( Figure 4C ). A more recent report showed the dual role of neutrophils in tumour-draining lymph nodes (LN) during head and neck cancer (HNC) progression ( 177 ). In these settings, neutrophils transmigrate and shape T cells activation in a stage-dependent manner, with neutrophils acquiring APC-like features and promoting T cell anti-tumour activity in metastasis-free patients, while at a later stage, neutrophils acquire PD-L1 expression and suppress T cell activation.…”

Section: Neutrophils In Cancermentioning

confidence: 99%

Neutrophil diversity in inflammation and cancer

et al. 2023

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Neutrophils are the most abundant circulating leukocytes in humans and the first immune cells recruited at the site of inflammation. Classically perceived as short-lived effector cells with limited plasticity and diversity, neutrophils are now recognized as highly heterogenous immune cells, which can adapt to various environmental cues. In addition to playing a central role in the host defence, neutrophils are involved in pathological contexts such as inflammatory diseases and cancer. The prevalence of neutrophils in these conditions is usually associated with detrimental inflammatory responses and poor clinical outcomes. However, a beneficial role for neutrophils is emerging in several pathological contexts, including in cancer. Here we will review the current knowledge of neutrophil biology and heterogeneity in steady state and during inflammation, with a focus on the opposing roles of neutrophils in different pathological contexts.

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“…Given these findings, exploring specific pro-tumorigenic NET components in glioma may reveal novel disease markers and therapeutic targets in glioma. However, it is important to mention that neutrophils also exert numerous anti-tumor functions by killing tumor cells and T enhancing anti-tumor -cell responses (141). Therefore, the dilemma of inhibiting NETs and inadvertently attenuating beneficial-in this case, tumor suppressive-neutrophil functions must be carefully considered.…”

Section: Gliomamentioning

confidence: 99%

Neutrophil extracellular traps in central nervous system pathologies: A mini review

Shafqat

Eddin²,

Adi³

et al. 2023

Front. Med.

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Neutrophils are the first cells to be recruited to sites of acute inflammation and contribute to host defense through phagocytosis, degranulation and neutrophil extracellular traps (NETs). Neutrophils are rarely found in the brain because of the highly selective blood-brain barrier (BBB). However, several diseases disrupt the BBB and cause neuroinflammation. In this regard, neutrophils and NETs have been visualized in the brain after various insults, including traumatic (traumatic brain injury and spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis and Alzheimer’s disease), and neoplastic (glioma) causes. Significantly, preventing neutrophil trafficking into the central nervous system or NET production in these diseases alleviates brain pathology and improves neurocognitive outcomes. This review summarizes the major studies on the contribution of NETs to central nervous system (CNS) disorders.

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

Cited by 47 publications

References 55 publications

Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil

Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil

Neutrophil diversity in inflammation and cancer

Neutrophil extracellular traps in central nervous system pathologies: A mini review

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