A5048778565- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- T-cell and B-cell Immunology
- Immune cells in cancer
- Adolescent and Pediatric Healthcare
- Dermatology and Skin Diseases
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- interferon and immune responses
- Epigenetics and DNA Methylation
- Macrophage Migration Inhibitory Factor
- Bipolar Disorder and Treatment
- Immune Response and Inflammation
- Barrier Structure and Function Studies
- Antimicrobial Peptides and Activities
- Neuroblastoma Research and Treatments
- RNA Research and Splicing
- vaccines and immunoinformatics approaches
- melanin and skin pigmentation
- Cell Adhesion Molecules Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Allergic Rhinitis and Sensitization
University Hospital Bonn
2017-2025
Peter Doherty Institute
2017-2024
The University of Melbourne
2017-2024
University of Bonn
2015-2024
Abstract Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using multifaceted approach systematically characterize FR as inhibitor Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism action. We also use investigate whether inhibition Gq an effective...
We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP-P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. demonstrate critical importance an eATP-P2X7-ASC-NALP3-inflammasome-IL18 pathway in antitumor activity mediated by enzyme blockade, rather than simply reducing adenosine as...
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, drug However, how MITF suppressed in vivo...
Whereas CD4 + T cells conventionally mediate antitumor immunity by providing help to CD8 cells, recent clinical studies have implied an important role for cytotoxic in cancer immunity. Using orthotopic melanoma model, we provide a detailed account of antitumoral cell responses and their regulation major histocompatibility complex class II (MHC II) the skin. Intravital imaging revealed prominent interactions with tumor debris-laden MHC host antigen-presenting that accumulated around nests,...
Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and number neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, immunotherapy is thought be less effective tumors low frequencies such as neuroblastoma, neuroendocrine tumor early childhood poor outcome high-risk disease group. However, spontaneous regressions paraneoplastic syndromes seen...
RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition its positive regulatory role, also restricts recognition through unknown mechanisms, as patients deficient suffer from neuroinflammation. Consistent with this, mice lacking exhibit interferon-dependent neuroinflammation, impaired hematopoiesis, and splenomegaly....
Background Immune responses against tumors are subject to negative feedback regulation. checkpoint inhibitors (ICIs) blocking Programmed cell death protein 1 (PD-1), a receptor expressed on T cells, or its ligand PD-L1 have significantly improved the treatment of cancer, in particular malignant melanoma. Nevertheless, and durability variables, suggesting that additional critical mechanisms exist need be targeted improve therapeutic efficacy. Methods We used different syngeneic melanoma mouse...
Epigallocatechin-3-gallate (EGCG) has been proven effective in treating viral warts. Since anticarcinogenic as well anti-inflammatory properties are ascribed to the substance, its use evaluated context of different dermatoses. The effect EGCG on interface dermatitis (ID), however, not yet explored.In this study, we investigated an epidermal human vitro model ID.Via immunohistochemistry, lesional skin lichen planus patients and healthy were analysed concerning intensity interferon-associated...
To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from bloodstream and their route tumors. Using intravital microscopy in mouse models melanoma, we discovered that circulating cells preferably adhered extravasated at a distinct type venous blood vessel tumor vicinity, peritumoral vessels (PVVs). Other vascular structures were excluded as alternative routes melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors...
This protocol details the procedure for CRISPR-assisted insertion of epitopes (CRISPitope), a flexible approach generating tumor cells expressing model CD8+ T cell fused to endogenously encoded gene products choice. CRISPitope-engineered can be recognized by receptor-transgenic (TCRtg) that are widely used in immunology research. Using mice inoculated with cells, researchers investigate how choice target antigen immunotherapies influences treatment efficacy and resistance mechanisms. For...
The upregulation of inhibitory molecules is a major driver immune escape in cancer. In contrast, less known about the regulation T cell activating receptors within tumor microenvironment. Here, we describe that derived CD155, transmembrane glycoprotein immunoglobulin superfamily, downregulates receptor CD226 (DNAM-1) mouse and human CD8+ cells, leading to profound loss effector function cancer evasion. Mechanistically, CD155 drives internalisation through phosphorylation tyrosine 319...
<div>Abstract<p>We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP–P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. We demonstrate critical importance an eATP–P2X7–ASC–NALP3-inflammasome–IL18 pathway in antitumor activity mediated by enzyme blockade, rather than...
<p>Supplementary Methods, Figures, Legends and Tables</p>
<p>Supplementary Methods, Figures, Legends and Tables</p>
<div>Abstract<p>We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP–P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. We demonstrate critical importance an eATP–P2X7–ASC–NALP3-inflammasome–IL18 pathway in antitumor activity mediated by enzyme blockade, rather than...
Abstract Non-recirculating tissue-resident memory T (TRM) cells reside permanently in epithelial tissues where they are known to protect against infection. TRM have now been identified various human cancers correlate with improved patient outcomes, but the mechanisms through which may mediate protective tumour immunity remain unclear. Using a novel mouse model of transplantable cutaneous melanoma, we show that tumour-specific form spontaneously microenvironment cancer development...