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Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [scRNA-seq]

ABSTRACT: Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [scRNA-seq]

PROVIDER: PRJNA1255142 | ENA |

REPOSITORIES: ENA

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	SRR33308496_1.fastq.gz	Fastqsanger.gz
	SRR33308496_2.fastq.gz	Fastqsanger.gz

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Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [RNA-Seq]

Project description:Bone metastases remain incurable and respond poorly to immune checkpoint blockade (ICB) therapy. The impact of neutrophil maturation in cancer remains largely unknown, especially in refractory tumors including bone metastases. Here, we observed the predominance of immature neutrophils in the bone metastasis microenvironment of both mouse models and cancer patients. DKK1 induces the immature-like functional state in neutrophils, which exert robust immunosuppressive capabilities to inhibit anti-tumor response of CD8+ T cells. Mechanistically, driven by the DKK1-CKAP4-STAT6 signaling, Chil3 expression is identified and required for the immune suppression mediated by immature neutrophils in bone metastases. Moreover, using multiple syngeneic and human immune system (HIS) mouse models, we found that DKK1 blockade efficiently allows neutrophil maturation to improve the immune microenvironment, controls tumor progression, and enhances ICB therapy response in bone metastases. Thus, our findings uncover an essential role for immature neutrophils in cancer, especially in bone metastases, and propose a potential strategy modulating neutrophils to improve cancer immunotherapy.

2025-06-01 | GSE295537 | GEO

Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [scRNA-seq]

2025-06-01 | GSE295533 | GEO

Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [RNA-Seq]

Project description:Chil3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases [RNA-Seq]

| PRJNA1255145 | ENA

Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis

Project description:Neutrophils play a key role in the control of metastatic progression. Neutrophils are phenotypically heterogeneous and can exert either anti- or pro-metastatic functions. Here, we demonstrate that tumor cells capable of forming liver metastases induce an accumulation of neutrophils in the peripheral blood and liver parenchyma. Cancer cell-derived G-CSF, in concert with other factors, mobilizes immature low-density neutrophils that promote liver metastasis. In contrast, mature high-density neutrophils inhibit the formation of liver metastases. Transcriptomic and metabolomic analyses of high- and low- density neutrophils reveal engagement of numerous metabolic pathways specifically in low-density neutrophils. Low-density neutrophils exhibit enhanced global bioenergetic capacity, through their ability to engage mitochondrial-dependent ATP production, and remain capable of executing pro-metastatic neutrophil functions, including NETosis, under nutrient-deprived conditions. Together, these data reveal that distinct pro-metastatic neutrophil populations exhibit a high degree of metabolic flexibility, which facilitates metastatic progression and the formation of liver metastases.

2019-06-26 | GSE123669 | GEO

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

Project description:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.

2021-10-05 | GSE157789 | GEO

Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases

Project description:Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases

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Tumor-entrained neutrophils inhibit seeding in the pre-metastatic lung

Project description:Tumor-entrained neutrophils inhibit seeding in the pre-metastatic lung

| PRJNA144243 | ENA

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

Project description:Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

| PRJNA662785 | ENA

Human immature neutrophils as a functional biomarker of systemic vascular pathologies

Project description:Human immature neutrophils as a functional biomarker of systemic vascular pathologies

| PRJNA622530 | ENA

Monocytes and neutrophils

Project description:Monocytes and neutrophils are both myeloid cells that have the same progenitor, the granulocyte macrophage precursor (GMP). Neutrophils are mature innate cells that are phagocytes and can degranulate to mount an immune response, whereas monocytes are immature pluripotent cells that can differentiate into macrophages and dendritic cells that can phagocytose and present antigen. To compare the expression pattern and validate samples purity by comparing expression data with previously generated data for monocytes and neutrophils, we isolated monocytes (CD45+ CD64+ CD14+ CD16-) and neutrophils (CD66b+ CD16+) from eight healthy volunteers.

2014-03-20 | E-MTAB-1573 | biostudies-arrayexpress

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