A5029878963- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- High Altitude and Hypoxia
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Lymphatic System and Diseases
- Pancreatic function and diabetes
- Liver physiology and pathology
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Adipose Tissue and Metabolism
- Medical Imaging Techniques and Applications
- Mesenchymal stem cell research
- Eicosanoids and Hypertension Pharmacology
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatic and Hepatic Oncology Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Protein Degradation and Inhibitors
University of Zurich
2017-2025
University of Duisburg-Essen
2006-2023
Paris Cardiovascular Research Center
2014-2022
Inserm
2014-2022
Université Paris Cité
2015-2022
Klinikum Arnsberg
2020
VIB-KU Leuven Center for Cancer Biology
2019
University of Minho
2019
University of Lausanne
2019
Ludwig Cancer Research
2019
Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which characterized by expression of inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and progressive loss function. The recent development therapies targeting PD-1 CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, regulation expression, thereby...
T cells can inhibit tumor growth, but their function in the microenvironment is often suppressed. Many solid tumors exhibit abundant macrophage infiltration and low oxygen tension, yet how hypoxic conditions may affect innate immune role progression poorly understood. Targeted deletion of hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) macrophages a progressive murine model breast cancer resulted reduced although vascular endothelial growth factor-A levels...
Hypoxic response and inflammation both involve the action of hypoxia-inducible transcription factors HIF-1α HIF-2α. Previous studies have revealed that HIF-α proteins are in a number aspects similarly regulated post-translationally. However, functional interrelationship these two isoforms remains largely unclear. The polarization macrophages controls functionally divergent processes; one is nitric oxide (NO) production, which turn controlled part by HIF factors. We show here can be...
Inflammatory mediators activate the transcriptional complex HIF-1 (hypoxia-inducible factor-1), key regulator of hypoxia-induced gene expression. Here we report that bacterial LPS (lipopolysaccharide) induces HIF-1α mRNA expression and protein accumulation in human monocytes as well non-differentiated differentiated cells monocytic cell line THP-1 under normoxic conditions. hypoxia synergistically activated HIF-1. Whereas increased through activation a NF-κB (nuclear factor κB) site promoter...
Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by ability macrophages adopt a proangiogenic proregenerative M2-like phenotype. Mechanistically, lactate secretion ECs lowered levels in muscle. Addition pfkfb3-deficient restored polarization an...
Infiltration of Foxp3(+) regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. reg supposedly suppress locally an effective anti-tumor immune response within tissues, although the precise mechanism by which infiltrate still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed cells, regulates immunological control guiding into in tumor-derived vascular endothelial growth factor (VEGF). demonstrate for first time...
Immune cell dysfunction within the tumor microenvironment (TME) undermines control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, temporal dynamics, mechanistic underpinning and functional significance NK compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic cellular analyses, to interrogate fate intratumoral cells. We reveal that cells rapidly lose...
Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer infiltrate areas. Cellular adaptation to low oxygen is mediated Hypoxia-inducible (HIFs). We found that deletion HIF-1α in NK inhibited growth despite impaired killing. Tumours developing these conditions were characterised high-density network immature vessels, severe...
Natural killer (NK) cells are tightly regulated by the JAK-STAT signaling pathway and cannot survive in absence of STAT5. We now report that STAT5-deficient NK can be rescued overexpression BCL2. Our experiments define STAT5 as a master regulator NK-cell proliferation lytic functions. Although generally responsible for killing tumor cells, promote formation producing enhanced levels angiogenic factor VEGFA. The importance VEGFA produced was verified with conditional knockout cells. show...
In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed coordinated role 2 major mediators efferocytosis, myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling skewing inflammatory response after myocardial infarction.We generated double-deficient mice for Mertk Mfge8 (Mertk(-/-)/Mfge8(-/-)) challenged...
Abstract The fibrogenic response in tissue-resident fibroblasts is determined by the balance between activation and repression signals from tissue microenvironment. While molecular pathways which transforming growth factor-1 (TGF-β1) activates pro-fibrogenic mechanisms have been extensively studied are recognized critical during fibrosis development, factors regulating TGF-β1 signaling poorly understood. Here we show that macrophage hypoxia suppresses excessive a heart via oncostatin-m (OSM)...
Angiogenesis is a key feature of liver fibrosis. Although sinusoidal remodeling believed to contribute fibrogenesis, the impact angiogenesis on resolution fibrosis remains undefined. Myeloid cells, particularly macrophages, constantly infiltrate fibrotic and can profoundly sinusoids. We observe that development associated with decreased hepatic vascular endothelial growth factor (VEGF) expression as well rarefication scar. In contrast, characterized by rise in VEGF levels revascularization...
A key adaptation to environmental hypoxia is an increase in erythropoiesis, driven by the hormone erythropoietin (EPO) through what traditionally thought be primarily a renal response. However, both neurons and astrocytes (the largest subpopulation of glial cells CNS) also express EPO following ischemic injury, this response known ameliorate damage brain. To investigate role as component systemic hypoxia, we created astrocyte-specific deletions murine genes encoding hypoxia-inducible...
Glioma growth and progression are characterized by abundant development of blood vessels that highly aberrant poorly functional, with detrimental consequences for drug delivery efficacy.The mechanisms driving this vessel dysmorphia during tumor understood.Using longitudinal intravital imaging in a mouse glioma model, we identify dynamic sprouting functional morphogenesis branched network characterize the initial growth, dramatically changing to expansion, leakage, loss branching complexity...
Abstract During skin injury, immune response and repair mechanisms have to be coordinated for rapid regeneration the prevention of microbial infections. Natural Killer (NK) cells infiltrate hypoxic lesions Hypoxia-inducible transcription factors (HIFs) mediate adaptation low oxygen. We demonstrate that mice lacking factor (HIF)-1α isoform in NK show impaired release cytokines Interferon (IFN)-γ Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) as part a blunted response. This...
Gut innate lymphoid cells (ILCs) show remarkable phenotypic diversity, yet microenvironmental factors that drive this plasticity are incompletely understood. The balance between NKp46+, IL-22–producing, group 3 ILCs (ILC3s) and interferon (IFN)-γ–producing 1 (ILC1s) contributes to gut homeostasis. mucosa is characterized by physiological hypoxia, adaptation low oxygen mediated hypoxia-inducible transcription (HIFs). However, the impact of HIFs on ILC phenotype homeostasis not well Mice...
Tissue injury initiates a complex series of events that act to restore structure and physiological homeostasis. Infiltration inflammatory cells vascular remodeling are both keystones this process. However, the role inflammation angiogenesis in general and, more specifically, significance cell-derived VEGF context unclear. To determine clinically relevant chronically inflamed injury, pulmonary fibrosis, we deleted VEGF-A gene myeloid cells. In model fibrosis mice, deletion resulted...
Abstract Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation low is regulated by oxygen‐sensitive transcription factors, the hypoxia‐inducible factors (HIFs). function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated predominantly glycolytic, but programs that ensure maintenance enigmatic. By combining in situ metabolomic transcriptomic analyses murine cells, our study defines...