A5037572599- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Respiratory viral infections research
- CAR-T cell therapy research
- Respiratory Support and Mechanisms
- Medical Imaging and Pathology Studies
- Brain Metastases and Treatment
- Melanoma and MAPK Pathways
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Cancer therapeutics and mechanisms
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- Lipid metabolism and biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Inhalation and Respiratory Drug Delivery
University of Bergen
2014-2025
Inserm
2017-2021
Institut Gustave Roussy
2017-2021
Université Paris-Saclay
2019-2021
Université Paris-Sud
2017-2020
École Pratique des Hautes Études
2019-2020
The University of Texas Southwestern Medical Center
2017-2018
BerGenBio (Norway)
2017-2018
Haukeland University Hospital
2017-2018
Southwestern Medical Center
2017-2018
IntroductionAcquired cancer therapy resistance evolves under selection pressure of immune surveillance and favors mechanisms that promote drug through cell survival evasion. AXL receptor tyrosine kinase is a mediator phenotypic plasticity suppression tumor immunity, expression associated with diminished long-term in wide range malignancies, including NSCLC.MethodsWe aimed to investigate the underlying AXL-mediated acquired first- third-generation small molecule EGFR inhibitors (EGFRi)...
Immune resistance may arise from both genetic instability and tumor heterogeneity. Microenvironmental stresses such as hypoxia various mechanisms promote carcinoma cell plasticity. AXL, a member of the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase family, is widely expressed in human cancers increasingly recognized for its role plasticity drug resistance. To investigate immune resistance, we studied multiple lung cancer clones derived model hypoxia-induced that exhibited mesenchymal or...
Epithelial to mesenchymal transition (EMT) is a well-characterized process of cell plasticity that may involve metabolic rewiring. In cancer, EMT associated with malignant progression, tumor heterogeneity, and therapy resistance. this study, we investigated the role succinate dehydrogenase (SDH) as potential key regulator EMT.Associations between SDH subunits were explored in gene expression data from breast cancer patient cohorts, followed by in-depth studies suppression mediator cultured...
The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts understand pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding cell type-specific cytopathology and its impact on cellular tropism. Furthermore, novel SARS-CoV-2 mutations tropism, alternative routes entry, co-infections, virus replication kinetics along respiratory tract remains be explored in improved...
Glioblastomas (GBMs) are lethal brain cancers that resistant to current therapies. We investigated the cytotoxicity of human allogeneic NK cells against patient-derived GBM in vitro and vivo, as well mechanisms mediating their efficacy. demonstrate KIR2DS2 immunogenotype were more potent killers, notwithstanding absence inhibitory killer Ig-like receptor (KIR)-HLA ligand mismatch. FACS-sorted enriched KIR2DS2(+) cell subpopulations retained significantly high levels CD69 CD16 when contact...
Complex in vitro respiratory models, including air-liquid interface (ALI) transwell cultures and airway organoids, have emerged as promising tools for studying human virus infections. These models address several limitations of conventional two-dimensional cell line animal models. However, the lack standardized protocols application these infection studies limits possibilities comparing results across different research groups. Therefore, we applied a collaborative approach to harmonize...
Resistance to temozolomide (TMZ) is due in part enhanced DNA repair mediated by high expression of O6-methyl guanine methyltransferase (MGMT) that often characterised unmethylated promoter. Here, we investigated pre-treatment glioblastoma (GBM) cells with the 26S-proteasome inhibitor bortezomib (BTZ) as a strategy interfere MGMT and thus sensitise them TMZ.Cell lines patient GBM-derived were examined vitro, latter also implanted orthotopically into NOD-SCID C.B.-Igh-1b/lcrTac-Prkdc mice...
Increased glycolytic activity is a hallmark of cancer initiation and progression often observed in non-small cell lung (NSCLC). Pyruvate dehydrogenase (PDH) complex acts as gatekeeper between glycolysis oxidative phosphorylation, activation PDH known to inhibit activity. As part standard therapeutic regimen, patients with NSCLC harboring oncogenic mutations the epidermal growth factor receptor (EGFR) are treated EGFR tyrosine kinase inhibitors (EGFR TKIs). Independent good initial response,...
Tumor hypoxia is relevant for tumor growth, metabolism, resistance to chemotherapy and metastasis. We have previously shown that hyperoxia, using hyperbaric oxygen treatment (HBOT), attenuates growth shifts the phenotype from mesenchymal epithelial (MET) in DMBA-induced mammary model. This study describes effect of HBOT on angiogenesis, efficacy metastasis a triple negative MDA-MB-231 breast cancer model, evaluates positive BT-474 model.5 x 105 cells were injected s.c. groin area NOD/SCID...
The receptor tyrosine kinase AXL is associated with epithelial plasticity in several solid tumors including breast cancer and AXL-targeting agents are currently clinical trials. We hypothesized that a driver of stemness traits by co-option regulatory function normally reserved for stem cells. AXL-expressing cells human mammary ducts co-expressed markers multipotency, inhibition abolished colony formation self-maintenance activities while promoting terminal differentiation vitro. Axl-null...
The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism drives therapy failure. Here we provide evidence specific microenvironments impose non-sporadic expression proteins related to epithelial plasticity and drug resistance. Microarrays robotically printed combinatorial known composition were used make cell-based functional associations between microenvironments, which design-inspired by normal tumor-burdened...
The lack of inadequate preclinical models remains a limitation for cancer drug development and is primary contributor to anti-cancer failures in clinical trials. Heterotypic multicellular spheroids are three-dimensional (3D) spherical structures generated by self-assembly from aggregates two or more cell types. Compared traditional monolayer culture models, the organization cells into 3D tissue-like structure favors relevant physiological conditions with chemical physical gradients as well...
Introduction AXL receptor expression is proposed to confer immune-checkpoint inhibitor (ICI)-resistance in non-small cell lung cancer (NSCLC) patients. We sought interrogate conjunction with mutational and tumor-microenvironmental features uncover predictive mechanisms of resistance ICI-treated NSCLC Methods Tumor samples from 111 patients treated ICI-monotherapy were analyzed by immunohistochemistry for tumor- immune-AXL expression. Subsets whole-exome sequencing (n = 44) imaging mass...
TPS43 Background: Activation of the receptor tyrosine kinase AXL has a profound suppressive effect on innate immune system. is overexpressed multiple cell types in tumour microenvironment including dendritic cells, NK cells and tumour-associated macrophages. signalling supports escape by downregulating activity, modulating efferocytosis as well favouring an immunosuppressive chemokine profile M-MDSC expansion. prevalent tumours resistant to anti-PD-1 therapy (Hugo, 2016). Axl expression...
Introduction: Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway an emerging strategy accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize by abolishing autophagy survival signals augment DNA damage apoptosis. Methods: P3 patient-derived cells, as well tumour cell lines U87, HF66, A172, T98G were investigated for clonogenic...
Patient-derived organoids have revolutionized biomedical research and therapies by "transferring the patient into Petri dish". In vitro access to human lung representing distal tissue, i.e. alveolar organoids, would facilitate pertaining a wide range of medical conditions might open for future approach individualized treatment.We propose protocol derive single biopsy towards both bronchiolar organoids. By modulating Wnt pathway, we obtained differential gene expression main markers subtypes,...
Abstract The AXL receptor tyrosine kinase is associated with poor overall survival in a wide spectrum of cancers including lung and breast adenocarcinomas. signaling an important regulator tumor plasticity related to epithelial-to-mesenchymal transition (EMT) stem cell traits that drive metastasis drug resistance. Signaling via also key suppressor the anti-tumor innate immune response, expressed on several cells microenvironment natural killer (NK) tumor-associated macrophages. Hence resides...