Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils [bulk RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1139250 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29935906.fastq.gz | Fastqsanger.gz | |||
| SRR29935907.fastq.gz | Fastqsanger.gz | |||
| SRR29935908.fastq.gz | Fastqsanger.gz | |||
| SRR29935909.fastq.gz | Fastqsanger.gz |
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Project description:Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils.
| PRJNA1139246 | ENA
Project description:Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils. Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, we show that neutrophils which are trained to acquire these anti-tumorigenic functions both enhance secretory granule production and increase expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.
2025-06-04 | PXD054085 | Pride
Project description:Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils [scRNA-seq]
| PRJNA1139251 | ENA
Project description:Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils. Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFkB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, neutrophils that are trained to acquire these anti-tumorigenic functions, acquire enhanced secretory granule production and increased expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.
2025-06-04 | GSE272922 | GEO
Project description:Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils. Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFkB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, neutrophils that are trained to acquire these anti-tumorigenic functions, acquire enhanced secretory granule production and increased expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.
2025-06-04 | GSE272921 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-06-04 | GSE272923 | GEO
Project description:Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils. Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, we show that neutrophils which are trained to acquire these anti-tumorigenic functions both enhance secretory granule production and increase expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.
2025-07-08 | PXD055726 | Pride
Project description:Neutrophils are critical for effective anti-fungal immune responses. However, in fungal sepsis neutrophils undergo a phenotypical (Ly6G downregulation) and functional alteration (defective ROS production), impairing their anti-fungal capacity. Therefore we wish to characterize the neutrophils in septic mice transcriptionally to describe their role in driving sepsis. We included several control groups. Mice that lack T cells (TCRaKO mice) have increased resistance to the infection and their neutrophils appear unaltered. We identified G-CSF and DNA/histones to be responsible for affecting granulopoiesis, as rG-CSF and Clodronate liposomes combined expand Ly6Glow neutrohils in naive mice.
2021-10-01 | GSE160301 | GEO
Project description:Cell mediated cytotoxicity plays important roles in host immune defence and cancer immunosurveillance. Current technologies that study cell cytotoxicity are target cell centric and lack the capability to identify and isolate cytotoxic effector cells. We developed the Multiplexed Identification of Cytotoxic Cell assay (PAINTKiller), a novel flow cytometry compatible method for direct identification and sorting of cytotoxic effector cells. We demonstrate that this technique can accurately identify cytotoxic effector cells which can be isolated, expanded and retained its superior cytotoxic capability. This technique can also be easily combined with other flow cytometry complementary assays, cell sorting and sequencing. The results indicate that PAINTKiller assay will be a powerful tool to uncover the determinants of functional immune response and will be of significant interest for cell therapy manufacturing workflow.
2023-06-14 | GSE207508 | GEO
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