A5026470819- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Bladder and Urothelial Cancer Treatments
- Platelet Disorders and Treatments
- Cardiac tumors and thrombi
- Venous Thromboembolism Diagnosis and Management
- Kruppel-like factors research
- Galectins and Cancer Biology
- Ferroptosis and cancer prognosis
- Genital Health and Disease
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Fibroblast Growth Factor Research
- Extracellular vesicles in disease
- Glioma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammatory Biomarkers in Disease Prognosis
- Monoclonal and Polyclonal Antibodies Research
- Tryptophan and brain disorders
- IL-33, ST2, and ILC Pathways
- Peptidase Inhibition and Analysis
Uppsala University
2016-2024
Science for Life Laboratory
2016-2023
Oncode Institute
2023
The Netherlands Cancer Institute
2023
Alligator Bioscience (Sweden)
2019
University of Manchester
2019
Novo Nordisk (Denmark)
2019
Life & Brain (Germany)
2019
Abstract Gliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) in clinical development for solid tumors, but yet to be evaluated glioma. Here, we demonstrate that systemic delivery of αCD40 preclinical glioma models induces the formation tertiary lymphoid structures (TLS) proximity meningeal tissue. In treatment-naïve patients, presence TLS correlates with increased T cell infiltration. However, hypofunctional...
Glioblastomas are aggressive brain tumors that largely immunotherapy resistant. This is associated with immunosuppression and a dysfunctional tumor vasculature, which hinder T cell infiltration. LIGHT/TNFSF14 can induce high endothelial venules (HEVs) tertiary lymphoid structures (TLS), suggesting its therapeutic expression could promote recruitment. Here, we use cell-targeted adeno-associated viral (AAV) vector to express LIGHT in the glioma vasculature (AAV-LIGHT). We found systemic...
Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in cell content. Orthogonally, spatial imaging mass cytometry shows enrichment human recurrent compared matched glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak...
Checkpoint blockade of CTLA‐4 results in long‐lasting survival benefits metastatic cancer patients. However, patients treated with have suffered from immune‐related adverse events, most likely due to the breadth induced T‐cell activation. Here, we investigated efficacy a local low‐dose anti‐CTLA‐4 administration for treatment subcutaneous or orthotopic murine bladder 49 (MB49) carcinoma C57BL/6 mice. When MB49 tumors were grown s.c., peritumoral (p.t.) injection was equally effective as...
Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor β-positive pericytes to blood vessels. The endothelium is an essential source PDGFB this process. Platelets constitute major reservoir and are continuously activated the tumor microenvironment, exposing tumors plethora factors contained platelet granules. Here, we show that vascular function, as well pericyte coverage significantly impaired mice with conditional knockout platelets. A lack platelets...
Compromised vascular integrity facilitates extravasation of cancer cells and promotes metastatic dissemination. CD93 has emerged as a target for anti-angiogenic therapy, but its importance in cancers not been evaluated. Here, we demonstrate that participates maintaining the endothelial barrier reducing Primary melanoma growth was hampered CD93-/- mice dissemination increased, associated with disruption adherens tight junctions tumor elevated expression matrix metalloprotease 9 (MMP9) at...
// Luuk van Hooren 1, * , Maria Georganaki Hua Huang 1 Sara M. Mangsbo # Anna Dimberg Department of Immunology, Genetics and Pathology, Science for Life Laboratory, The Rudbeck Uppsala University, Uppsala, Sweden These first authors contributed equally to the work have Correspondence to: Dimberg, email: anna.dimberg@igp.uu.se Keywords: CD40, sunitinib, MDSC, endothelial activation, T-cell Received: November 11, 2015 Accepted: June 12, 2016 Published: July ABSTRACT CD40-activating...
CD40-stimulating immunotherapy can elicit potent anti-tumor responses by activating dendritic cells and enhancing T-cell priming. Tumor vessels orchestrate recruitment during immune response, but the effect of on tumor endothelial has not been evaluated. Here, we have investigated how transcriptionally respond to isolating from agonistic CD40 mAb- or isotype-treated mice bearing B16-F10 melanoma, performing RNA-sequencing. Gene set enrichment analysis revealed that mAb therapy increased...
Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 able induce VEGF-like signaling, which contributes angiogenesis. Furthermore, studies have demonstrated an immunosuppressive function of through effects on both effector and regulatory T cells. Elevated expression secretion been shown in many types, high serum levels connected poor prognosis cancer...
Abstract Background Tumor vessels in glioma are molecularly and functionally abnormal, contributing to treatment resistance. Proteins differentially expressed can change vessel phenotype be targeted for therapy. ELTD1 (Adgrl4) is an orphan member of the adhesion G-protein-coupled receptor family upregulated has been suggested as a potential therapeutic target. However, role regulating function glioblastoma poorly understood. Methods expression human gliomas its association with patient...
Bladder cancer, one of the most prevalent malignancies worldwide, remains hard to classify due a staggering molecular complexity. Despite plethora diagnostic tools and therapies, it is outline key steps leading up transition from high-risk non–muscle-invasive bladder cancer (NMIBC) muscle-invasive (MIBC). Carcinogen-induced murine models can recapitulate urothelial carcinogenesis natural anti-tumor immunity. Herein, we have developed profiled novel model progressive NMIBC based on 10 weeks...
Abstract CD40-activating immunotherapy has potent anti-tumor effects due to its ability activate dendritic cells and induce cytotoxic T-cell responses. However, efficacy is limited by accumulation of immunosuppressive in the tumor endothelial anergy induced pro-angiogenic growth factors. Here, we show that combining agonistic CD40 monoclonal antibody (mAb) therapy with vascular targeting using tyrosine kinase inhibitor sunitinib significantly decrease improve survival B16.F10 melanoma T241...
Abstract Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (αCD40) in clinical development for solid but yet to be evaluated glioma. Here, systemic delivery of αCD40 led cytotoxic T cell dysfunction and impaired the response immune checkpoint inhibitors preclinical glioma models. This was associated with an accumulation suppressive CD11b + B cells. However, also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated...
Abstract CTLA-4 blockade as well CD40 agonistic therapy comes with adverse events when administrated systemically to patients. Whereas anti-CD40 is associated both cytokine release and liver toxicity, leads auto-immune manifestations. Cytokine affects the maximum tolerated dose (MTD) for anti-CD40, thereby hampering anti-tumor responses. patients localized bladder cancer respond immunotherapy in form of BCG, they suffer high relapse frequencies toxicity. Patients a more advanced disease have...
<div>Abstract<p>Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor β–positive pericytes to blood vessels. The endothelium is an essential source PDGFB this process. Platelets constitute major reservoir and are continuously activated the tumor microenvironment, exposing tumors plethora factors contained platelet granules. Here, we show that vascular function, as well pericyte coverage significantly impaired mice with conditional knockout...
<p>Antibody concentration and blocking conditions</p>
<p>Data from endothelial cell qPCR array.</p>
<p>Supplementary methods: Primer sequences</p>
<p>Data from endothelial cell qPCR array.</p>
<p>Supplementary methods: Primer sequences</p>