- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Gastric Cancer Management and Outcomes
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Functional Brain Connectivity Studies
- Liver Diseases and Immunity
- Long-Term Effects of COVID-19
- Esophageal Cancer Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Dementia and Cognitive Impairment Research
- Renal and related cancers
- COVID-19 and Mental Health
- Traumatic Brain Injury Research
- Colorectal Cancer Treatments and Studies
- Liver Disease Diagnosis and Treatment
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
University Hospital of Basel
2023-2025
Hospital Base
2025
University of Basel
2023-2025
Martin Luther University Halle-Wittenberg
2019-2024
ETH Zurich
2022-2024
Luther University
2023
University Medical Center Hamburg-Eppendorf
2019
Universität Hamburg
2019
University Medical Center of the Johannes Gutenberg University Mainz
2018
Institute of Medical Microbiology and Hygiene
2018
Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory associated with SARS-CoV-2 infection, shares clinical features toxic shock syndrome, which is triggered by bacterial superantigens. Superantigen specificity for different Vβ chains results skewing, whereby T cells specific and diverse antigen are overrepresented the cell receptor (TCR) repertoire. Here, we characterized TCR repertoire of MIS-C patients found profound expansion TCRβ variable gene 11-2 (TRBV11-2), up to...
Tissue-resident memory-like T H 17 cells are clonally expanded in bronchoalveolar lavage fluid of patients with severe COVID-19.
Post-acute sequelae of COVID-19 (PASC) are long-term consequences SARS-CoV-2 infection that can substantially impair the quality life. Underlying mechanisms ranging from persistent viruses to innate and adaptive immune dysregulation have been discussed. Here, we profiled plasma 181 individuals cohort study for digital health research in Germany (DigiHero), including after mild moderate with or without PASC uninfected controls. We focused on soluble factors related monocyte/macrophage biology...
<h3>Importance</h3> In metastatic esophagogastric adenocarcinoma (EGA), the addition of programmed cell death 1 (PD-1) inhibitors to chemotherapy has improved outcomes in selected patient populations. <h3>Objective</h3> To investigate efficacy trastuzumab and PD-1 with cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) or FOLFOX first-line treatment advanced<i>ERBB2</i>-positive EGA. <h3>Design, Setting, Participants</h3> This phase 2 multicenter, outpatient, randomized clinical trial...
Background In patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration. Methods We treated 43 predominantly RAS/BRAF wild-type mCRC on a phase II trial combining chemotherapy the epidermal growth factor receptor antibody cetuximab programmed cell death ligand 1 (PD-L1) avelumab. performed next-generation gene panel sequencing for mutational typing of tumors...
Although natural killer (NK) cells are recognized for their modulation of immune responses, the mechanisms by which human NK mediate regulation unclear. Here, we report that expression leukocyte antigen (HLA)-DP, a ligand activating cell receptor NKp44, is significantly upregulated on CD8
Importance Adding immune checkpoint inhibitors to chemotherapy has been associated with improved outcomes in metastatic esophagogastric adenocarcinoma, but treatment combinations and optimal patient selection need be established. Objective To investigate the efficacy tolerability of programmed cell death ligand 1 (PDL-1) inhibitor avelumab paclitaxel plus ramucirumab. Design, Setting, Participants This multicenter, single-group, phase 2 nonrandomized controlled trial was conducted among...
The concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which a rarity in cancer. B receptors (BCR) mature lymphoid malignancies are exceptional that they harbor tumor-specific-stereotyped sequences the form point drive self-engagement BCR and autologous signaling. Here, we use light chain neoepitope defined by characteristic mutation (IGLV3-21R110) for selective poor-risk subset chronic lymphocytic leukemia (CLL) with...
Background Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in &gt;50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates checkpoint inhibitor monotherapy remain limited strategies to strengthen tumor-directed immune responses are needed. Objective The FOCUS trial designed...
Background and Aims Autoimmune hepatitis (AIH) is a chronic liver disease that regularly relapses when immunosuppression tapered. It thought to be driven by T‐cells, whereas the etiologic impact of an apparently deregulated B lineage system, as evidenced hypergammaglobulinemia autoantibodies, remains elusive. We set out investigate T cell repertoires supporting inflammation in AIH. Approach Results receptor (TCR/BCR) human leukocyte antigen (HLA) next‐generation immunosequencing were used...
In parasite and viral infections, aberrant B cell responses can suppress germinal center reactions thereby blunting long-lived memory may provoke immunopathology including autoimmunity. Using COVID-19 as model, we set out to identify serological, cellular, transcriptomic imprints of pathological linked autoreactive cells at single-cell resolution. We show that excessive plasmablast expansions are prognostically adverse correlate with autoantibody production but do not hinder the formation...
Abstract We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play role in NK cell biology, we reasoned these may impact cell-mediated CLL immunity. Indeed, our experiments significantly decreased degranulation capacity primary cells from expressing low levels SLAMF1 and SLAMF7. the signature was strongly associated unmutated...
Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers post transcriptional gene silencing events. Up until now, relevance this for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile plasma active convalescent COVID-19 patients presence small circulating RNAs. The existence SARS-CoV-2 derived in samples mild severe cases...
The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging variants. Therefore, aiming at strong B cell somatic hypermutation increase antibody affinity - not only high titers is a priority when utilizing vaccines are targeted individual variants since may offer some flexibility compensate strain-individual mutations. Here, we developed next-generation sequencing based SARS-CoV-2 tracking protocol...
Abstract Viral vectors have successfully modified T cells to express chimeric antigen receptors (CAR), leading clinical approvals. However, their high cost and regulatory challenges hinder rapid broad translation. Here, we demonstrate that our lentivirally (LV) manufactured R110-CAR cells, targeting a leukemia neoepitope, can also be engineered using non-viral Sleeping Beauty (SB) transposition with minimal-sized DNA vectors. Flow cytometry single-cell sequencing was used compare the two...
Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against self-antigens, but how these autoreactive cells relate to tissue pathology remains unclear. Here we perform single-cell transcriptomic and receptor analyses of circulating, self-antigen-specific from patients with AILD identify a subset liver-autoreactive distinct B-helper transcriptional profile characterized by PD-1, TIGIT HLA-DR expression. These share clonal relationships expanded intrahepatic...
<p>Supplementary Figure 1: The duration of response to various therapy lines for patients in the Ipi arm is depicted. For each line therapy, (DOR) indicated if applicable. Active represented by an arrow, and dashed arrows are used who were lost follow-up. Monotherapy with trastuzumab (T), ramucirumab (R), radiotherapy (#), or surgery (*) also indicated.</p>
<p>Supplementary Figure 3: Low NLR defines patients with superior survival in the Ipi arm.</p>
<p>Supplementary Figure 2: Emotional distress and tumor burden do not explain the systemic inflammatory signature.</p>
<div>Abstract<p>Anti–PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma, but long-term survival remains limited. In this study, we report extended follow-up data from INTEGA trial (NCT03409848), which investigated efficacy anti–PD-1 nivolumab, FOLFOX (FOLFOX arm) comparison a chemotherapy-free regimen involving anti–CTLA-4 ipilimumab (Ipi first-line setting for disease. The 12-month overall (OS)...
<p>Supplementary Figure 4: PFS in selected patients and overall survival of NLR > 5 patients. (A) months is shown for by CPS ≥ 1, HER2-3+, < within the Ipi arm (n=12). Median was 20.9 months. (B) Final vs FOLFOX >5 preselected Number at risk are indicated. Log-rank test performed (B).</p>