A5000189121- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Viral Infections and Outbreaks Research
- Single-cell and spatial transcriptomics
- Cancer, Stress, Anesthesia, and Immune Response
- Cell Adhesion Molecules Research
- Cancer Genomics and Diagnostics
- Animal Virus Infections Studies
- HER2/EGFR in Cancer Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Cells and Metastasis
- Inflammatory mediators and NSAID effects
- Magnesium in Health and Disease
- T-cell and B-cell Immunology
- Viral Infections and Vectors
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
University Hospital of Basel
2018-2025
University of Basel
2018-2024
University Hospital Regensburg
2018-2020
Freiwillige Akademische Gesellschaft
2020
Immune checkpoint blockade (ICB) has substantially improved the prognosis of patients with cancer, but majority experiences limited benefit, supporting need for new therapeutic approaches. Up-regulation sialic acid–containing glycans, termed hypersialylation, is a common feature cancer-associated glycosylation, driving disease progression and immune escape through engagement Siglec receptors on tumor-infiltrating cells. Here, we show that tumor sialylation correlates distinct states reduced...
Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective immunity is thought to require cDC1s sustain T cell responses within tumors, but it poorly understood how this function regulated and whether its subversion contributes immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE2) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability locally orchestrate CD8+ responses. Mechanistically, cAMP signaling downstream...
Abstract Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for cell immunotherapies. generated with this resemble tumor-infiltrating phenotypic and transcriptional level. Using targeted pooled CRISPR-Cas9 screen individual gene knockout validation experiments, we uncover sorting nexin-9 (SNX9) as mediator of exhaustion. Upon TCR/CD28 stimulation, deletion SNX9 in CD8...
T cell–directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen clinical benefit immunotherapies. Here, we demonstrate that therapeutic targeting interferon-γ (IFN-γ)–interleukin-12 (IL-12) pathway relies on ability a population natural killer (NK) cells with tissue-resident traits orchestrate an antitumor microenvironment. In particular, used engineered adenoviral platform as tool for...
Interactions between sialylated glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors have been recently described as potential new immune checkpoint that can be targeted to improve anticancer immunity. Myeloid cells reported express a wide range of different Siglecs; however, their expression functions on cancer-associated dendritic (DCs) were not fully characterized. We found classical conventional DCs (cDCs) from cancer patient samples high several inhibitory...
Programmed death ligand 1 (PD-L1) expression is an efficient strategy of tumor cells to escape immunological eradiation. However, only little known about the factors that affect cellular levels. Here we assessed PD-L1 on different breast cancer cell lines under standard in vitro culture conditions and as a function Epirubicin or Paclitaxel treatment. Moreover, evaluated immunodeficient mice well humanized (i.e., presence human immune system). We found highest levels JIMT-1 MDA-MB-231 cells....
Highlights•Microtubule destabilization in dendritic cells drives DC maturation and T cell activation•GEF-H1 is released from microtubules, leading to its release triggers the RhoA-JNK-c-Jun signaling axis AP-1 transcriptional response•GEF-H1 critical for maturation, antigen cross-presentation, anti-tumor immunitySummaryDendritic (DC) activation a step responses. Certain chemotherapeutics can influence function. Here we demonstrate that chemotherapy capable of microtubule has direct effects...
Abstract Diabetes mellitus (DM) significantly increases the risk for cancer and progression. Hyperglycemia is defining characteristic of DM tightly correlates with a poor prognosis in patients cancer. The hexosamine biosynthetic pathway (HBP) emerging as pivotal cascade linking high glucose, tumor progression, impaired immune function. Here we show that enhanced glucose flow through HBP drives progression evasion by increasing O-GlcNAcylation tumor-associated macrophages (TAM). Increased...
Abstract Introduction: Immune checkpoint inhibitors (ICI) revolutionized the treatment of cancer. However, most patients do not respond to currently available therapies, or become refractory, which demonstrates need for development novel therapeutic strategies. The transmembrane protein Neuropilin-1 (NRP1) interacts with various receptors and ligands contributes an immunosuppressive tumor microenvironment (TME) through multiple mechanisms. NRP1 facilitates migration associated macrophages...
Adenovirus-mediated combination gene therapies have shown promising results in vaccination or treating malignant and genetic diseases. Nevertheless, an efficient system for the rapid assembly incorporation of therapeutic genes into high-capacity adenoviral vectors (HCAdVs) is still missing. In this study, we developed iMATCH (integrated modular HCAdVs) platform, which enables generation production HCAdVs encoding combinations high quantity purity within 3 weeks. Our cloning facilitates up to...
Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8+ T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these viruses delivering a self-antigen in heterologous prime-boost regimen induce CTL up to 50% the circulating CD8 cell pool. This attack eliminates established solid...
Background Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses significant fraction of patients. This lack long-term efficacy may be due poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) programmed cell death ligand 1 (PD-L1), aiming overcome resistance anti-PD-L1 monoclonal therapy....
Abstract Background Antibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab that targets the human epidermal growth factor related receptor 2 (HER2) is one of greatest stories this field. For decades, trastuzumab treatment regimens are significantly improving prognosis HER2-positive breast patients both metastatic (neo-) adjuvant setting. Nevertheless, ≥ 50% treated experience de - novo or...
<h3>Background</h3> Modulation of the immune system by checkpoint inhibitors (ICI) has become an important strategy for treatment cancer. However, majority patients does not respond to available therapies, indicating a need innovative targets and new modalities. The membrane-bound multi domain protein neuropilin-1 (NRP1) is involved in cell migration, survival neoangiogenesis. It furthermore can mediate suppression anti-tumor responses attracting suppressive myeloid cells into tumor...
e14592 Background: While the introduction of immune checkpoint inhibitors (ICIs) is considered as a breakthrough in cancer therapy, large proportions patients still do not respond or develop resistance, indicating need for new targets and therapies to provide long-term therapeutic benefits. Neuropilin-1 (NRP1) membrane-bound multi domain protein expressed by different cell types tumor microenvironment. NRP1 promotes migration, survival, angiogenesis via distinct domains. Moreover, it...
<h3>Background</h3> Unleashing anti-tumor immune responses by checkpoint inhibitors is an efficient approach for the treatment of cancer. Still, majority patients does not respond to currently available therapies, highlighting need development novel therapeutic strategies. Neuropilin-1 (NRP1) a transmembrane protein that interacts with numerous receptors and ligands contributes protumorigenic, immunosuppressive tumor microenvironment (TME). NRP1 supports migration macrophages into TME,...
Abstract Immune checkpoint blockade (ICB) has significantly improved the prognosis of cancer patients, but majority experience limited benefit, evidencing need for new therapeutic approaches. Upregulation sialic acid-containing glycans, termed hypersialylation, is a common feature cancer-associated glycosylation, driving disease progression and immune escape via engagement Siglec-receptors on tumor-infiltrating cells. Here, we show that tumor sialylation correlates with distinct states...
<div>Abstract<p>Diabetes mellitus (DM) significantly increases the risk for cancer and progression. Hyperglycemia is defining characteristic of DM tightly correlates with a poor prognosis in patients cancer. The hexosamine biosynthetic pathway (HBP) emerging as pivotal cascade linking high glucose, tumor progression, impaired immune function. Here we show that enhanced glucose flow through HBP drives progression evasion by increasing O-GlcNAcylation tumor-associated macrophages...
<p>Supplementary Figures 1-8</p>
<p>Supplementary Figures 1-8</p>
<div>Abstract<p>Diabetes mellitus (DM) significantly increases the risk for cancer and progression. Hyperglycemia is defining characteristic of DM tightly correlates with a poor prognosis in patients cancer. The hexosamine biosynthetic pathway (HBP) emerging as pivotal cascade linking high glucose, tumor progression, impaired immune function. Here we show that enhanced glucose flow through HBP drives progression evasion by increasing O-GlcNAcylation tumor-associated macrophages...
<h3>Background</h3> Immune checkpoint inhibitors (ICI) are considered as a breakthrough in cancer therapy, however only subset of patients actually responds to current treatments, indicating strong remaining medical need. Locked nucleic acid (LNA) modified antisense oligonucleotides (ASOs) allow for specific target knockdown after systemic injection without delivery agents. The membrane bound multi domain protein neuropilin-1 (NRP1) is promising therapeutic target, since it has been...
The oncologic spectrum for the clinical utilization of checkpoint inhibitors (CI) expands rapidly. Clinical trials with CI in breast cancer (BC) report an overall response rate up to 19% durable responses and tolerable safety profiles. Improved understanding immunogenicity BC under simultaneously applied therapies, e.g., cytotoxic treatments, would help develop more individual therapeutic strategies further increase rates.