A5064779191- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Glycosylation and Glycoproteins Research
- Lung Cancer Research Studies
- Immune cells in cancer
- Inflammatory Biomarkers in Disease Prognosis
- Cancer, Lipids, and Metabolism
- Planarian Biology and Electrostimulation
- Magnesium in Health and Disease
- Inflammatory mediators and NSAID effects
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Chemokine receptors and signaling
- Nanoparticles: synthesis and applications
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Graphene and Nanomaterials Applications
University Hospital of Basel
2018-2024
LMU Klinikum
2023-2024
Ludwig-Maximilians-Universität München
2023-2024
München Klinik
2024
University of Basel
2019-2023
University Hospital of Bern
2018
University of Bern
2018
First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) pattern-recognition receptors binding a range of sialoglycan ligands, which appear function as self-associated molecular patterns (SAMPs) that suppress autoimmune...
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...
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 Purpose: PD-(L)1–blocking antibodies have clinical activity in metastatic non–small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms primary resistance may allow prediction response identification new targetable pathways. Experimental Design: Peripheral blood mononuclear cells were collected from 35 with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels,...
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....
A genome-wide PiggyBac transposon-mediated screen and a resistance in PIK3CAH1047R-mutated murine tumor model reveal NF1 loss mammary tumors resistant to the phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor alpelisib. Depletion of PIK3CAH1047R breast cancer cell lines patient-derived organoid shows that reduces sensitivity PI3Kα inhibition correlates with enhanced glycolysis lower levels reactive oxygen species (ROS). Unexpectedly, antioxidant N-acetylcysteine (NAC) sensitizes...
Introduction Naïve T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start to proliferate and generate effector initiate a functional immune response. Metabolic reprogramming is essential meet the biosynthetic demands differentiation process, failure do so can promote development hypofunctional exhausted cells. Methods Here we used 13C metabolomics transcriptomics study metabolism CD8+ their complete course from naïve over...
Abstract T-cell exhaustion poses a significant barrier to the efficacy of immunotherapies. In past decade, immune checkpoint blockade (ICB) has been leading strategy prevent or reverse exhaustion. Although ICB yields promising clinical outcomes in patients with cancer, its impact on reinvigoration is often short-lived. High-throughput genomic tools, including CRISPR screening along single-cell RNA and chromatin accessibility sequencing may point toward new therapeutic avenues. However, their...
Background T cell-based immunotherapies including immune checkpoint blockade and chimeric antigen receptor cells can induce durable responses in patients with cancer. However, clinical efficacy is limited due to the ability of cancer evade surveillance. While have been primary focus immunotherapy, recent research has highlighted importance natural killer (NK) directly recognizing eliminating tumor playing a key role set-up an effective adaptive response. The remarkable potential NK for...