Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Sept. 20, 2024
Language: Английский
Cancer Cell, Journal Year: 2023, Volume and Issue: 41(4), P. 757 - 775.e10
Published: April 1, 2023
Language: Английский
Citations
121
Nature Reviews Materials, Journal Year: 2021, Volume and Issue: 7(5), P. 355 - 371
Published: Nov. 23, 2021
Language: Английский
Citations
120
MedComm, Journal Year: 2022, Volume and Issue: 3(3)
Published: Aug. 19, 2022
Abstract Evidence shows that neutrophils can protect the host against pathogens in multiple ways, including formation and release of neutrophil extracellular traps (NETs). NETs are web‐like structures composed fibers, DNA, histones, various granule proteins. capture kill pathogens, bacteria, viruses, fungi, protozoa. The process NET is called NETosis. According to whether they depend on nicotinamide adenine dinucleotide phosphate (NADPH), NETosis be divided into two categories: “suicidal” “vital” However, components, elastase, myeloperoxidase, cell‐free cause a proinflammatory response potentially severe diseases. Compelling evidence indicates link between pathogenesis number diseases, sepsis, systemic lupus erythematosus, rheumatoid arthritis, small‐vessel vasculitis, inflammatory bowel disease, cancer, COVID‐19, others. Therefore, targeting products critical for treating diseases linked with Researchers have discovered several inhibitors, such as toll‐like receptor inhibitors reactive oxygen species scavengers, prevent uncontrolled development. This review summarizes mechanism NETosis, receptors associated pathology NETosis‐induced NETosis‐targeted therapy.
Language: Английский
Citations
100
Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 277 - 312
Published: Aug. 11, 2022
Neutrophil extracellular trap (NET) formation, first described in 2004 as a previously unknown strategy of neutrophils to fight microbes, has attracted an increasing interest the research community. NETs are formed when externalize their decondensed chromatin together with content from azurophilic granules. In addition role defense against have been implicated mediators pathology sterile inflammation, such cancer and autoimmunity, potential therapeutic targets is actively explored. However, targeting challenging since beneficial effects removal need be balanced harmful loss function microbial defense. Moreover, depending on stimuli or species, can via distinct mechanisms not always made up same components, making direct comparisons between various studies challenging. This review focuses cancer-associated pathology, thrombosis, organ dysfunction, metastasis. Different strategies target NETs, by either preventing formation degrading existing ones, also discussed.
Language: Английский
Citations
97
Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)
Published: Aug. 28, 2022
Immune checkpoint inhibitors targeting programmed cell death protein 1, death-ligand and cytotoxic T-lymphocyte-associated 4 provide deep durable treatment responses which have revolutionized oncology. However, despite over 40% of cancer patients being eligible to receive immunotherapy, only 12% gain benefit. A key understanding what differentiates response from non-response is better defining the role innate immune system in anti-tumor immunity tolerance. Teleologically, myeloid cells, including macrophages, dendritic monocytes, neutrophils, initiate a invading pathogens tissue repair after pathogen clearance successfully accomplished. tumor microenvironment (TME), these cells are hijacked by imprinted furthering propagation dissemination. Major advancements been made field, especially related heterogeneity their function TME at single level, topic that has highlighted several recent international meetings 2021 China Cancer Immunotherapy workshop Beijing. Here, we an up-to-date summary mechanisms major facilitate immunosuppression, enable growth, foster plasticity, confer therapeutic resistance. We discuss ongoing strategies compartment preclinical clinical settings include: (1) altering composition within TME; (2) functional blockade immune-suppressive cells; (3) reprogramming acquire pro-inflammatory properties; (4) modulating via cytokines; (5) therapies; (6) emerging targets such as Siglec-15, TREM2, MARCO, LILRB2, CLEVER-1. There significant promise cell-based immunotherapy will help advance immuno-oncology years come.
Language: Английский
Citations
93
Trends in Microbiology, Journal Year: 2022, Volume and Issue: 31(3), P. 280 - 293
Published: Nov. 5, 2022
Language: Английский
Citations
90
Cancer Communications, Journal Year: 2022, Volume and Issue: 43(2), P. 225 - 245
Published: Nov. 8, 2022
Neutrophil extracellular traps (NETs) are considered significant contributors to cancer progression, especially metastasis. However, it is still unclear whether NETs involved in hepatitis B virus (HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation management for hepatocellular carcinoma (HCC). In this study, we aimed investigate the functional mechanism of HBV-related their significance. A total 175 HCC patients with without HBV infection 58 healthy controls were enrolled study. measured tissue specimens, freshly isolated neutrophils blood serum from these patients, correlation circulating levels malignancy was evaluated. The by which modulates formation explored using cell-based studies. addition, vitro vivo experiments further performed clarify on growth metastasis HCC. We observed an elevated level specimens those infected HBV. facilitated both vivo, mainly dominated increased angiogenesis, epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinases (MMPs)-induced (ECM) degradation NETs-mediated trapping. Inhibition generation DNase 1 effectively abrogated NETs-aroused HBV-induced S100A9 accelerated NETs, mediated activation toll-like receptor (TLR4)/receptor advanced glycation end products (RAGE)-reactive oxygen species (ROS) signaling. Further, circulatory found correlate viral load, TNM stage status HCC, identified could predict extrahepatic metastasis, area under ROC curve (AUC) 0.83 90.3% sensitivity 62.8% specificity at a cutoff value 0.32. Our findings indicated that RAGE/TLR4-ROS signaling resulted abundant formation, subsequently cells. More importantly, exhibited as alternative biomarker predicting
Language: Английский
Citations
79
Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4546 - 4566.e27
Published: Sept. 27, 2023
Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors substantial numbers. However, their precise functions different cancer types remain incompletely understood, including brain microenvironment. We therefore investigated neutrophils tumor tissue of glioma metastasis patients, with matched peripheral blood, herein describe first in-depth analysis neutrophil phenotypes these tissues. Orthogonal profiling strategies humans mice revealed that tumor-associated (TANs) differ significantly from blood have a prolonged lifespan immune-suppressive pro-angiogenic capacity. TANs exhibit distinct inflammatory signature, driven by combination soluble mediators necrosis factor alpha (TNF-ɑ) Ceruloplasmin, which is more pronounced versus glioma. Myeloid cells, macrophages, emerge at core this network pro-inflammatory mediators, supporting concept critical myeloid niche regulating overall suppression human tumors.
Language: Английский
Citations
78
Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)
Published: April 19, 2022
Abstract Cytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E 2 (PGE ) production in cells with pre-existing COX-2 activity. Screening a compound library of 1280 approved drugs, find all classes chemotherapy drugs enhance transcription whilst arresting proliferation. Genetic manipulation its gene promoter region uncover how augmented COX-2/PGE activity post-treatment profoundly alters the inflammatory properties chemotherapy-treated vivo. Pharmacological inhibition boosts efficacy combination PD-1 blockade. Crucially, immunogenic breast model, only triple unleashes significantly reduces relapse spontaneous metastatic spread an adjuvant setting. Our findings suggest upregulation by dying acts as major barrier to therapy-driven immunity strategy improve immunotherapy combinations.
Language: Английский
Citations
70
Science Immunology, Journal Year: 2023, Volume and Issue: 8(80)
Published: Feb. 3, 2023
Neutrophils, the most abundant innate immune cells, function as crucial regulators of adaptive system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within tissue environment. Here, using mouse models breast cancer lungs, we show that, although neutrophils isolated from bone marrow (BM) blood minimally immunosuppressive, lung-infiltrating robustly suppressive both T cells and natural killer (NK) cells. We found that this tissue-specific immunosuppressive capacity exists steady state is reinforced by tumor-associated inflammation. Acquisition potent immunosuppression activity was endowed lung-resident stroma, specifically CD140a + mesenchymal (MCs) via prostaglandin-endoperoxide synthase 2 (PTGS2), rate-limiting enzyme for prostaglandin E (PGE ) biosynthesis. MC-specific deletion Ptgs2 pharmacological inhibition PGE receptors reversed lung neutrophil–mediated mitigated metastasis vivo. These stroma–targeting strategies substantially improved therapeutic efficacy adoptive cell–based immunotherapy treating disease mice. Collectively, our results reveal immunoregulatory effects induced tissue-resident stroma targeting stromal factors represents an effective approach to boost immunity against disease.
Language: Английский
Citations
64