Susanne Dettwiler
A5087137618- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Glioma Diagnosis and Treatment
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Occupational and environmental lung diseases
- Cell Image Analysis Techniques
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Pleural and Pulmonary Diseases
- Renal cell carcinoma treatment
- DNA Repair Mechanisms
- Myofascial pain diagnosis and treatment
- Cancer, Lipids, and Metabolism
- Protease and Inhibitor Mechanisms
- PARP inhibition in cancer therapy
- Botulinum Toxin and Related Neurological Disorders
- Laser Applications in Dentistry and Medicine
- Cancer, Stress, Anesthesia, and Immune Response
- Immune Cell Function and Interaction
University Hospital of Zurich
2008-2024
University of Zurich
2012-2023
Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine chemokine assays from serum at baseline event onset indicated aberrant T cell activity with differential expression type I III immune signatures. This was in line finding an increase proportion CD4+ cells IL-17A peripheral blood using flow cytometry. Multiplex immunohistochemistry spatial transcriptomics...
PURPOSE CD276 (B7-H3) is an immunoregulatory protein that plays important role in the inhibition of T-cell function. overexpressed on a variety human solid cancer cells with limited expression normal tissues, making it appealing target for innovative immunotherapy approaches. Pleural mesothelioma (PM) highly aggressive disease need new treatment options. Our objective was to investigate multicenter PM cohort European Thoracic Oncology Platform Mesoscape project and correlate results...
Background. Despite its clinical promise in non-solid tumor, immunotherapy is yet to show significant efficacy for brain tumors including pediatric diffuse midline glioma (DMG). This indicated the need fully explore DMG immune tumor microenvironment (TME). Method. Whole brains (49 DMGs, 20 non-DMG, 10 non-malignant) from 79 patients were used establish a tissue microarray (918 cores) representing primary, metastatic, and adjacent healthy sites. CellDIVE MxIF multiplex assay was probe 33 cell...
Biorespositories of formalin-fixed and paraffin-embedded (FFPE) or fresh frozen human tissues from malignant diseases generated as integral part the diagnostic workup in many pathology departments have been pivotal resources for translational cancer studies. However, such tissue biobanks traditionally contained only non-viable specimens thus cannot enable functional assays discovery validation therapeutic targets assessment drug responses resistance to treatment. To overcome these...
Immune checkpoint inhibitory (ICI) therapy represents a novel approach in variety of cancers, with impressive survival benefit. With ICIs, however, new spectrum immune related adverse events (irAE) including life threatening hypohysitis has emerged. This autopsy study aimed to investigate inflammatory cells, PD-1 and PD-L1 expression cases patients who developed hypophysitis involvement other organs. We analysed 6 patients, were treated ICIs hypophysitis. Two received an additional...
Abstract Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy design neopeptides through single amino acid mutations enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well in silico HLA-binding predictions autologous HLA molecules were used identify candidate neopeptides. Subsequently, HLA-anchor placements deduce putative T-cell receptor...
PARP inhibitors (PARPi) are increasingly used in breast cancer therapy, including high-grade triple-negative (TNBC) treatment. Varying treatment responses and PARPi resistance with relapse currently pose limitations to the efficacy of therapy. The pathobiological reasons why individual patients respond differently poorly understood. In this study, we analyzed expression PARP1, main target PARPi, normal tissue, cancer, its precursor lesions using human tissue microarrays covering a total 824...
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Abstract BACKGROUND Diffuse midline glioma (DMG) is a fatal childhood brain cancer with survival rate of less than one year from diagnosis. Pharmacological approaches and immunotherapy have failed to make clinical impact. Incomplete understanding the tumor microenvironment (TME) associated antigens contributed observed poor prognosis. Therefore, mapping TME urgently needed. METHODS Whole brains were collected at autopsy 80 pediatric subjects, including patients diagnosed DMG (n=50), GBM...
<title>Abstract</title> Immune checkpoint inhibitors (ICIs) are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events (irAEs). Proteomic analysis and multiplex cytokine/chemokine assay from serum at baseline irAEs onset in 82 patients indicated aberrant T-cell activity with differential expression Type I III immune signatures. This was line an increase proportions monocytes decrease IL-17A producing CD4+ T-cells peripheral blood...
Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better biomarkers needed. The ribosomal protein S6 a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in synthesis cell proliferation. In previous studies, low phosphorylated (pS6) immunoreactivity was significantly correlated longer progression-free survival (PFS) overall (OS) PM patients. We aimed to correlate pS6...
Botulinum toxin type A (BTX-A) injections in masseter muscle can alleviate tightness and aching pain caused by idiopathic masticatory myalgia, a subform of the myofascial syndrome. Yet injection procedure (number, amount) is currently empirical. In this ex vivo study, we determined feasibility using contrast-free ultrasound imaging to visualize short-term injectate propagation. Ultrasound annotations BTX-A spread N = 12 porcine muscles were compared with histopathology excised masseter....
<p>Designed mutations increase the stimulatory strength of D-neopeptides above N-peptides. (A) TILs were stimulated with 5 μM class I-peptides, including N-peptides and D-neopeptides, for days. replicate wells tested proliferation, proliferation was measured by 3H-thymidine incorporation assay. In each group, their corresponding are included, designed mutated positions highlighted in red box. The blue dotted line indicates mean value no peptide control. plus three standard deviations...
<p>Over-/highly expressed genes in the primary glioblastoma when compared with cohort TCGA Database.</p>
<p>Predicted TSA/TAA-derived N-peptides and D-neopeptides</p>
<p>Peripheral blood T cell responses to v-peptides increase with repetitive vaccination. (A) PBMCs were collected 3 weeks after the 2nd peptide cocktail vaccination, and CD45RA-negative stimulated 4 μg/mL Tetanus toxoid, 2 μM CEF II pool or 5 for 7 days. 5-10 replicate wells tested proliferation, proliferation measured by 3H-thymidine incorporation assay. before vaccination used as reference. The strength is depicted stimulation index (SI). red dotted line indicates a stimulatory...
<p>PBMCs collected before vaccination show low/no response to candidate vaccine peptides. (A) The nomenclature of the N-peptides and D-neopeptides. I or II indicate if peptides were chosen/designed for HLA class -II binding; MUT/RNA/GBM indicates a naturally mutated peptide (MUT), derivation from over-/highly expressed genes (RNA) known glioblastoma (GBM) targets; X number peptide; 0 1 had been artificially (1) not (0); (’) that contained amino acid. (B) PBMCs stimulated with 4 μg/mL...
<p>Vaccinated D-neopeptides activate tumor-infiltrating antitumor T cells. (A) Circos plots provide an overview of the frequencies Vβ-Jβ pairing in primary and recurrent tumors. (B) Surface TCR β chain expression D-neopeptide-specific CD4+ TCCs was analyzed using FACs.</p>
<p>Increased T lymphocyte infiltration in the recurrent compared to primary tumor. (A) CD3 immunohistochemical staining and (B) Three fields of view were selected counted CD3+ cells both perivascular peritumoral areas tumors using ImageJ. Scale bars are indicated figures.</p>