Article
Oncology
Sandra N. Freiberger, David Holzmann, Gregoire B. Morand, Martin Huellner, Mitchell P. Levesque, Reinhard Dummer, Viktor H. Koelzer, Niels J. Rupp
Summary: This study investigates novel biomarkers in mucosal melanoma that predict response to combined ipilimumab and nivolumab immunotherapy. The results suggest that the testis antigens CTAG1B (NY-ESO-1), MAGE-A3, and MAGE-A4 are predominantly expressed in responding tumors, and could potentially be used for future routine diagnostics to predict treatment outcomes.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Sarah A. Nadeau, Timothy G. Vaughan, Christiane Beckmann, Ivan Topolsky, Chaoran Chen, Emma Hodcroft, Tobias Schaer, Ina Nissen, Natascha Santacroce, Elodie Burcklen, Pedro Ferreira, Kim Philipp Jablonski, Susana Posada-Cespedes, Vincenzo Capece, Sophie Seidel, Noemi Santamaria de Souza, Julia M. Martinez-Gomez, Phil Cheng, Philipp P. Bosshard, Mitchell P. Levesque, Verena Kufner, Stefan SchmutzSchmutz, Maryam Zaheri, Michael Huber, Alexandra Trkola, Samuel Cordey, Florian Laubscher, Ana Rita Goncalves, Sebastien Aeby, Trestan Pillonel, Damien Jacot, Claire Bertelli, Gilbert Greub, Karoline Leuzinger, Madlen Stange, Alfredo Mari, Tim Roloff, Helena Seth-Smith, Hans H. Hirsch, Adrian Egli, Maurice Redondo, Olivier Kobel, Christoph Noppen, Louis du Plessis, Niko Beerenwinkel, Richard A. Neher, Christian Beisel, Tanja Stadler
Summary: Genome sequencing of SARS-CoV-2 in Switzerland revealed the number and persistence of virus introductions. Border closures in Switzerland significantly reduced case introductions, with up to a 98% reduction during the strictest measures. The partial lockdown in 2020 also shortened the time for introductions to die out. The study demonstrates the importance of genome sequencing data in understanding transmission dynamics.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Mateusz S. Wietecha, David Lauenstein, Michael Cangkrama, Sybille Seiler, Juyoung Jin, Andreas Goppelt, Manfred Claassen, Mitchell P. Levesque, Reinhard Dummer, Sabine Werner
Summary: Healing wounds and cancers share similarities at the cellular and molecular levels. The specific roles of healing phases are poorly understood. By comparing gene expression patterns, it was found that a wound signature during the resolution phase is associated with more severe skin cancer. Comparison of early and late-phase wound fibroblasts with cancer-associated fibroblasts (CAFs) identified distinct subtypes of CAFs. These findings provide insights into wound-regulated genes and matrix patterns with prognostic potential in skin cancer.
Article
Oncology
Marlene Langenbach, Sophie Giesler, Stefan Richtsfeld, Sara Costa-Pereira, Lukas Rindlisbacher, Tobias Wertheimer, Lukas M. Braun, Geoffroy Andrieux, Sandra Duquesne, Dietmar Pfeifer, Nadine M. Woessner, Hans D. Menssen, Sanaz Taromi, Justus Duyster, Melani Boerries, Tilman Brummer, Bruce R. Blazar, Susana Minguet, Patrick Turko, Mitchell P. Levesque, Burkhard Becher, Rober Zeiser
Summary: Treatment of metastatic melanoma with immune checkpoint inhibitors (ICI) has high response rates, but resistance to ICI impacts patient survival. In this study, the role of MDM2 inhibition in enhancing ICI therapy was investigated using mouse models and patient-derived melanoma cells. MDM2 inhibition induced expression of IL15 and MHC-II in melanoma cells through p53 induction. This enhanced antitumor immunity and induced anti-melanoma immune memory. In patients, increased IL15 and MHC-II expression correlated with better prognosis in WT melanoma but not TP53-mutated melanoma.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
Florian Maerkl, Mohamed-Reda Benmebarek, Julius Keyl, Bruno L. Cadilha, Martina Geiger, Clara Karches, Hannah Obeck, Melanie Schwerdtfeger, Stefanos Michaelides, Daria Briukhovetska, Sophia Stock, Jakob Jobst, Philipp Jie Mueller, Lina Majed, Matthias Seifert, Anna-Kristina Kluever, Theo Lorenzini, Ruth Gruenmeier, Moritz Thomas, Adrian Gottschlich, Richard Klaus, Carsten Marr, Michael von Bergwelt-Baildon, Simon Rothenfusser, Mitchell P. Levesque, Markus Vincent Heppt, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: Melanoma is an immune sensitive disease, and immune check point blockade has shown activity. However, TIL therapy after ICB failure has shown promising efficacy, indicating the potential of cellular therapies. To overcome limitations of TIL treatment, a controlled adoptive cell therapy approach using synthetic agonistic receptors and bispecific antibodies targeting melanoma-associated antigens is proposed.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Alina Miriam Mueller, Elisabeth Victoria Goessinger, Sara Elisa Cerminara, Lisa Kostner, Margarida Amaral, Stephanie Marie Huber, Lea Pauline Passweg, Laura Garcia Moreno, Daniel Bodenmann, Michael Kunz, Mitchell Paul Levesque, Julia-Tatjana Maul, Phil Fang Cheng, Alexander Andreas Navarini, Lara Valeska Maul
Summary: The incidence of melanoma has been increasing rapidly worldwide, and Switzerland has one of the highest rates in Europe. UV radiation is a major risk factor for skin cancer. This study investigated UV protective behavior and melanoma awareness in high-risk cohorts for melanoma. The results showed that melanoma patients used higher sun protection factors (SPF) compared to at-risk patients, and higher education levels were associated with more frequent use of high SPF. However, higher education levels also correlated with increased annual sun exposure. Participation in the study resulted in improved sun protection behavior.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Nicolas Gonzalo Nunez, Fiamma Berner, Ekaterina Friebel, Susanne Unger, Nina Wyss, Julia Martinez Gomez, Mette-Triin Purde, Rebekka Niederer, Maximilian Porsch, Christa Lichtensteiger, Rafaela Kramer, Michael Erdmann, Christina Schmitt, Lucie Heinzerling, Marie-Therese Abdou, Julia Karbach, Dirk Schadendorf, Lisa Zimmer, Selma Ugurel, Niklas Kluemper, Michael Hoelzel, Laura Power, Stefanie Kreutmair, Mariaelena Capone, Gabriele Madonna, Lacin Cevhertas, Anja Heider, Teresa Amaral, Omar Hasan Ali, David Bomze, Florentia Dimitriou, Stefan Diem, Paolo Antonio Ascierto, Reinhard Dummer, Elke Jaeger, Christoph Driessen, Mitchell Paul Levesque, Willem van de Veen, Markus Joerger, Martin Frueh, Burkhard Becher, Lukas Flatz
Summary: In this study, a multi-omics approach was used to characterize the systemic immune compartment of melanoma or non-small cell lung cancer patients before and during immune checkpoint inhibitor (ICI) treatment. Potential predictive biomarkers for ICI-induced immune-related adverse events (irAEs) were identified, including early increase in CXCL9/CXCL10/CXCL11 and interferon-g (IFN-g) 1 to 2 weeks after treatment initiation, as well as early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells.
Article
Biochemistry & Molecular Biology
Marvin Thielert, Ericka C. M. Itang, Constantin Ammar, Florian A. Rosenberger, Isabell Bludau, Lisa Schweizer, Thierry M. Nordmann, Patricia Skowronek, Maria Wahle, Wen-Feng Zeng, Xie-Xuan Zhou, Andreas-David Brunner, Sabrina Richter, Mitchell P. Levesque, Fabian J. Theis, Martin Steger, Matthias Mann
Summary: Single-cell proteomics allows unbiased characterization of biological function and heterogeneity at the protein level. However, current limitations include proteomic depth, throughput, and robustness. In this study, we introduce a streamlined multiplexed workflow using mDIA to address these limitations. Our approach enables automated and complete dimethyl labeling of bulk or single-cell samples, without compromising proteomic depth. We also demonstrate the ability to quantify twice as many proteins per single cell compared to previous methods, and our workflow allows routine analysis of 80 single cells per day. Additionally, we combine mDIA with spatial proteomics to increase the throughput for microdissection and MS analysis, and successfully identify proteomic signatures of cells within distinct tumor microenvironments in primary cutaneous melanoma.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Markus Haake, Beatrice Haack, Tina Schaefer, Patrick N. Harter, Greta Mattavelli, Patrick Eiring, Neha Vashist, Florian Wedekink, Sabrina Genssler, Birgitt Fischer, Julia Dahlhoff, Fatemeh Mokhtari, Anastasia Kuzkina, Marij J. P. Welters, Tamara M. Benz, Lena Sorger, Vincent Thiemann, Giovanni Almanzar, Martina Selle, Klara Thein, Jacob Spaeth, Maria Cecilia Gonzalez, Carmen Reitinger, Andrea Ipsen-Escobedo, Kilian Wistuba-Hamprecht, Kristin Eichler, Katharina Filipski, Pia S. Zeiner, Rudi Beschorner, Renske Goedemans, Falk Hagen Gogolla, Hubert Hackl, Rogier W. Rooswinkel, Alexander Thiem, Paula Romer Roche, Hemant Joshi, Dirk Puehringer, Achim Woeckel, Joachim E. Diessner, Manfred Ruediger, Eugen Leo, Phil F. Cheng, Mitchell P. Levesque, Matthias Goebeler, Markus Sauer, Falk Nimmerjahn, Christine Schuberth-Wagner, Stefanie von Felten, Michel Mittelbronn, Matthias Mehling, Andreas Beilhack, Sjoerd H. van der Burg, Angela Riedel, Benjamin Weide, Reinhard Dummer, Joerg Wischhusen
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Henning Zelba, Armin Rabsteyn, Oliver Bartsch, Christina Kyzirakos, Simone Kayser, Marcel Seibold, Johannes Harter, Pauline Latzer, Dirk Hadaschik, Florian Battke, Alexander Golf, Matthew B. Rettig, Saskia Biskup
Summary: Localized prostate cancer can be cured, but metastatic castration-sensitive prostate cancer has a low survival rate. This study investigated the use of individualized neoantigen-derived peptide vaccination as a treatment option for mCSPC patients. The results showed that individualized vaccines can induce strong and durable immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Fabienne Frohlich, Egle Ramelyte, Patrick Turko, Andreas Dzung, Sandra N. Freiberger, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer
Summary: Although immunotherapy and targeted therapy have improved melanoma survival, some patients rapidly progress and decease within months after a stage IV diagnosis. This study aimed to find genetic alterations that predict short or long survival in melanoma patients and found that a clock-like mutational signature was associated with poor survival, while a UV mutational signature was prognostic for longer survival. These findings suggest that mutational signatures could be valuable prognostic markers for melanoma.
Article
Public, Environmental & Occupational Health
Jule Ayran, Carsten Koehler, Le Thi Kieu Linh, Gisela Schneider, Srinivas Reddy Pallerla, Florian Battke, Lisa Federle, Peter Martus, Peter G. Kremsner, Thirumalaisamy P. Velavan
Summary: Despite contact restrictions, population mobility remains the main reason for the spread of SARS-CoV-2. A model study in Tubingen, Germany evaluated the use of mandatory rapid diagnostic tests to reduce transmission. The study found a positive predictive value of 51% and identified the B.1.1.7 lineage as the predominant variant in positive samples.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Biology
Ulrike Lischetti, Aizhan Tastanova, Franziska Singer, Linda Grob, Matteo Carrara, Phil F. F. Cheng, Julia M. Martinez M. Gomez, Federica Sella, Veronika Haunerdinger, Christian Beisel, Mitchell P. Levesque
Summary: CITE-seq technology bridges the gap between RNA and protein in single-cell analysis, but its application to solid biopsies is limited. Applying CITE-seq to clinically relevant solid biopsies is an essential step in single-cell translational studies.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Oncology
Haley P. Wilson, Timothy J. Purwin, Claudia Capparelli, Phil F. Cheng, Mitch P. Levesque, Reinhard Dummer, Jessica Teh, Andrew E. Aplin
Article
Biochemical Research Methods
Linda Grob, Anne Bertolini, Matteo Carrara, Ulrike Lischetti, Aizhan Tastanova, Christian Beisel, Mitchell P. Levesque, Daniel J. Stekhoven, Franziska Singer
Summary: Recently, a new single-cell technology called CITE-seq has emerged, which can capture both gene expression and surface protein information from individual cells. This technology provides unprecedented insights into disease mechanisms, heterogeneity, and immune cell profiling. However, most existing single-cell profiling methods focus on either gene expression or antibody analysis, not both. In addition, current software suites are not easily scalable for analyzing multiple samples. To address these challenges, we developed gExcite, a comprehensive workflow that enables gene and antibody expression analysis as well as hashing deconvolution. Embedded in the Snakemake workflow manager, gExcite ensures reproducibility and scalability. We demonstrate the output of gExcite using a study of different dissociation protocols on PBMC samples.