Tobias Bald
A5025785991- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune cells in cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- Adenosine and Purinergic Signaling
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Mast cells and histamine
- S100 Proteins and Annexins
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Cutaneous Melanoma Detection and Management
- Cell Adhesion Molecules Research
- IL-33, ST2, and ILC Pathways
University Hospital Bonn
2013-2025
University of Bonn
2011-2025
QIMR Berghofer Medical Research Institute
2017-2024
Integrated Oncology (United States)
2022
University Medical Center
2022
University Hospital and Clinics
2022
University Hospital Magdeburg
2016-2021
CeMM Research Center for Molecular Medicine
2019
Ludwig Cancer Research
2019
University of St. Gallen
2019
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...
Infiltration of human melanomas with cytotoxic immune cells correlates spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade immune-inhibitory receptors in patients preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity cell-poor melanomas. Here, we show that primary Hgf-Cdk4(R24C) mice, which imitate poor outcome, escape IFN-induced surveillance editing. Peritumoral injections...
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...
Abstract Inflammation promotes phenotypic plasticity in melanoma, a source of non-genetic heterogeneity, but the molecular framework is poorly understood. Here we use functional genomic approaches and identify reciprocal antagonism between melanocyte lineage transcription factor MITF c-Jun, which interconnects inflammation-induced dedifferentiation with pro-inflammatory cytokine responsiveness melanoma cells favouring myeloid cell recruitment. We show that cytokines such as TNF-α instigate...
Evolution of tumor cell phenotypes promotes heterogeneity and therapy resistance. Here we found that induction CD73, the enzyme generates immunosuppressive adenosine, is linked to melanoma phenotype switching. Activating MAPK mutations growth factors drove CD73 expression, which marked both nascent full activation a mesenchymal-like state program. Proinflammatory cytokines like TNFα cooperated with signaling through c-Jun/AP-1 transcription factor complex activate by binding an intronic...
Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and ligand (PD-L1) require greater attention. Nectins nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation migration exert immunomodulatory functions pathophysiological conditions. Here, we show CD155 expression both malignant cells tumor-infiltrating myeloid humans mice. Cd155–/– mice displayed reduced tumor growth metastasis via DNAM-1 upregulation...
Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment vascular system. This was clearly demonstrated for netrin-1 via its interaction with receptors DCC and UNC5s. However, mainly based on shared homologies netrin-1, netrin-4 also play role in neuronal outgrowth developmental/pathological angiogenesis interactions receptors. Here, we present high-resolution structure netrin-4, which shows...
Abstract Elevated numbers of regulatory T cells (Treg) in patient tumors are known to inhibit efficient antitumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% depletion was achieved, resulting complete rejection transplanted HCmel12 melanomas a CD8+ T-cell–dependent way. contrast, 90% obtained BAC transgenic Foxp3.LuciDTR4 mice failed induce melanomas, demonstrating that...
Increasing evidence exists for the role of immunosuppressive adenosine in promoting tumor growth and spread a number cancer types, resulting poor clinical outcomes. In this study, we assessed whether CD73-adenosinergic pathway is active melanoma patients restricts efficacy clinically approved targeted therapies commonly mutated BRAFV600E melanoma. AJCC stage III patients, CD73 expression (the enzyme that generates adenosine) correlated significantly with presenting nodal metastatic melanoma,...
Resistance to anti-PD1-based immune checkpoint blockade (ICB) remains a problem for the treatment of metastatic melanoma. Tumor cells as well host myeloid can express ligand CD155 regulate cell function. However, effect tumor on context human melanoma has not been described. This observational study characterizes expression by tumors and correlates results with differences in features response ICB.Pretreatment specimens, from 155 patients treated ICB 50 BRAF/MEK-directed targeted therapy,...
Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain demand. Since anti-tumor activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as predictive on-treatment biomarker. In retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, CRP kinetics were stratified after start immunotherapy until weeks 4, 6, 12 follows: an doubling...
Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) and ILC1s. We identify population "liver-type" ILC1s with transcriptional, phenotypic, functional features distinct from those conventional liver-resident NK as well other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, do not activating receptor NKp80 or EOMES. Similar to cells, liver-type produce IFN-γ, TNF-α, GM-CSF;...