A5077920005- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Cutaneous Melanoma Detection and Management
- interferon and immune responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Single-cell and spatial transcriptomics
Deutschen Konsortium für Translationale Krebsforschung
2020-2025
Essen University Hospital
2020-2025
Heinrich Heine University Düsseldorf
2021-2025
Düsseldorf University Hospital
2021-2025
University of Duisburg-Essen
2020-2024
German Cancer Research Center
2020-2022
Understanding tumor resistance to T cell immunotherapies is critical improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels melanoma metastases before immune checkpoint blockade (ICB) correlated with nonresponsiveness poor clinical outcome. Patient-derived cells silenced escaped recognition by autologous CD8+ cells....
Recent studies have demonstrated HLA class II (HLA-II)-dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution HLA-II-loss tumors that escape T-cell activity and contribute to immunotherapy resistance.Melanoma from longitudinal metastases were studied for constitutive IFN-inducible HLA-II expression, sensitivity towards autologous cells, immune evasion loss. Clinical significance HLA-II-low was determined analysis transcriptomic data sets patients with...
Immune activation within the tumor is one promising approach to induce immune-mediated regression. Certain viruses including oncolytic like herpes simplex virus (HSV) and non-oncolytic such as lymphocytic choriomeningitis (LCMV) are potent tools tumor-specific immune activation, however not all types respond viro- and/or immunotherapy mechanisms explaining differences remain be defined. We used non-cytopathic LCMV in different human melanoma models found that cell lines produced high levels...
Immunotherapy is currently one of the most promising treatment options for malignant melanoma [1]. To uncover new immunological targets future approaches, single-cell transcriptomic and epigenomic analyses were performed on human primary (MM) melanocytic nevus (Nev) samples (Figure 1A). The detailed methods this study are described in Supplementary Material. MM Nev biopsies (Supplementary Figure S1; Table S1) analyzed by RNA sequencing (scRNA-seq) Assay Transposase-Accessible Chromatin...
Melanoma is a highly malignant tumor, that stands as the most lethal form of skin cancer and characterized by notable phenotypic plasticity intratumoral heterogeneity. involved in tumor growth, metastasis therapy resistance. Long non-coding RNAs (lncRNAs) could influence due to their regulatory function. However, role mode action are poorly studied. Here, we show relevance lncRNA GRASLND melanoma differentiation IFNγ signaling. knockdown revealed switching differentiated, melanocytic cells...
Background Immune-stimulatory agents, like agonists of the innate immune receptor RIG-I, are currently tested in clinical trials as an intratumoral treatment option for patients with unresectable melanoma, aiming to enhance anti-tumor T cell responses. Switching melanoma toward a dedifferentiated state has recently been linked and therapy resistance. It remains be determined whether RIG-I affect differentiation, potentially leading Methods Patient metastases-derived lines were treated...
<div>AbstractPurpose:<p>Recent studies have demonstrated HLA class II (HLA-II)–dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution HLA-II–loss tumors that escape T-cell activity and contribute to immunotherapy resistance.</p>Experimental Design:<p>Melanoma from longitudinal metastases were studied for constitutive IFN-inducible HLA-II expression, sensitivity towards autologous cells, immune evasion loss. Clinical significance...
<p>JAK inhibition downregulates HLA-II but not HLA-I or PD-L1 expression in melanoma cells</p>
<p>ConstHLA-II melanoma cells lack endogenous interferon expression</p>
<p>Homogeneous HLA-I and PD-L1 expression in consecutive melanoma samples from patient Ma-Mel-61</p>
<p>HLA-II expression in longitudinal melanoma samples</p>
<p>HLA-II APM transcript levels in melanoma biopsies from ICB-treated patients</p>
<div>Abstract<p>Purpose: Recent studies have demonstrated HLA class II (HLA-II)-dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution HLA-II-loss tumors that escape cell activity and contribute to immunotherapy resistance. Experimental Design: Melanoma from longitudinal metastases were studied for constitutive interferon-inducible HLA-II expression, sensitivity towards autologous cells, immune evasion loss. Clinical significance HLA-II-low was...
<p>Homogeneous HLA-I and PD-L1 expression in consecutive melanoma samples from patient Ma-Mel-61</p>
<p>ConstHLA-II melanoma cells lack endogenous interferon expression</p>
<p>No chromosomal alterations in the MHC region of HLA-II-loss JAK1/2 mutant melanoma cells</p>
<p>JAK inhibition downregulates HLA-II but not HLA-I or PD-L1 expression in melanoma cells</p>
<p>HLA-II APM transcript levels in melanoma biopsies from ICB-treated patients</p>
<p>HLA-II expression in longitudinal melanoma samples</p>
<p>CD4 T-cell sensitivity of constHLA-II melanoma cells</p>
<p>CD4 T-cell sensitivity of constHLA-II melanoma cells</p>
<p>No chromosomal alterations in the MHC region of HLA-II-loss JAK1/2 mutant melanoma cells</p>
<div>Abstract<p>Purpose: Recent studies have demonstrated HLA class II (HLA-II)-dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution HLA-II-loss tumors that escape cell activity and contribute to immunotherapy resistance. Experimental Design: Melanoma from longitudinal metastases were studied for constitutive interferon-inducible HLA-II expression, sensitivity towards autologous cells, immune evasion loss. Clinical significance HLA-II-low was...
<p>Homogeneous HLA-I and PD-L1 expression in consecutive melanoma samples from patient Ma-Mel-61</p>