Wertheimer Laboratory
About us
The Translational Cancer Immunology Lab aims to decode the intricate mechanism underlying the immunosuppressive tumor microenvironment leading to cancer progression and therapy resistance. Therefore, we employ advanced systems immunology and single-cell biology tools in our mission to develop improved and personalized cancer immunotherapies.
Research Topics
Deciphering Tumor Microenvironment Dynamics
A strong focus of our group is the deep investigation into the tumor microenvironment, particularly focusing on the cellular crosstalk in the tumor immune environment supporting cancer progression. Utilizing sophisticated preclinical models, including genetically engineered mouse models (GEMM), in combination with state-of-the art single cell and spatial technologies, we aim to identify targetable pathways by which, for example, regulatory T cells maintain their stability and function within the tumor setting and impair efficient anti-tumor immunity. The ultimate goal of these studies is to derive novel strategies for cancer immunotherapy.
Advancing Personalized Immunotherapy Strategies
Building on our foundational work, the second aim of our lab delves into the translational sphere. We utilize single-cell and spatial technologies, combined with computational analysis tools, to investigate the mechanisms underlying patient responses and resistance and relapse in the context of immunotherapy including allogeneic hematopoietic cell transplantation (allo-HCT), CAR-T cell and bispecific antibody therapy. Our objective is to leverage these insights to pioneer personalized immunotherapies, ultimately enhancing patient outcomes. This aspect of our research not only aims to uncover the complexities behind immunotherapy resistance but also seeks to identify predictive biomarkers for treatment efficacy, paving the way for customized therapeutic approaches.
TEAM
Head of Wertheimer Laboratory
Principal Investigator
Dr. Tobias Wertheimer
tobias.wertheimer@uniklinik-freiburg.de
Zentrum Translationale Zellforschung (ZTZ)
Breisacher Str. 115
D- 79106 Freiburg
Kornelia Fritsch
Lina Schlenke
- Wolfgang Huber, EMBL Heidelberg
- Nir Yosef, Weizmann Institute, Rehovot (Israel)
- Tilman Brummer, University of Freiburg
- Robert Zeiser, University Medical Center Freiburg
- Kimon Argyropoulos, Memorial Sloan Kettering Cancer Center, New York, USA
- Sonia Tugues, University of Zurich
- Burkhard Becher, University of Zurich
- Thorsten Zenz, University Hospital Zurich
- Guido Beldi, Inselspital Bern
- Dietmar Zaiss, University of Regensburg
- Kristina Maas-Bauer, University Medical Center Freiburg
- Natalie Köhler, University Medical Center Freiburg
1. Wertheimer, T., Zwicky, P., Rindlisbacher, L., Sparano, C., Vermeer, M., de Melo, B. M. S., Haftmann, C., Rückert, T., et al. IL-23 stabilizes an effector Treg cell program in the tumor microenvironment. Nat. Immunol. 25, 512–524 (2024) 10.1038/s41590-024-01755-7.
2. Nuñez, N. G., Schmid, J., Power, L., Alberti, C., Krishnarajah, S., Kreutmair, S., Unger, S., Blanco, S., …, Wertheimer, T. et al. High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity.
Nat. Immunol. 24, 941–954 (2023) 10.1038/s41590-023-01499-w.
3. Ho, J. N. H. G., Schmidt, D., Lowinus, T., Ryoo, J., Dopfer, E.-P., Gonzalo Núñez, N., Costa-Pereira, S., Toffalori, C., Punta, M., Fetsch, V., Wertheimer, T., et al. Targeting MDM2 enhances antileukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation. Blood 140, 1167–1181 (2022) 10.1182/blood.2022016082.
4. Wertheimer, T. & Tugues, S. IFN-λ: paving the road toward tissue protection in GVHD. Blood 138, 596–597 (2021) 10.1182/blood.2021012348.
5. Wertheimer, T., Velardi, E., Tsai, J., Cooper, K., Xiao, S., Kloss, C. C., Ottmüller, K. J., Mokhtari, Z., et al. Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration. Science Immunology. 3, eaal2736 (2018) 10.1126/sciimmunol.aal2736.
6. Velardi, E., Tsai, J. J., Radtke, S., Cooper, K., Argyropoulos, K. V., Jae-Hung, S., Young, L. F., Lazrak, A., …, Wertheimer, T., et al. Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat. Med. 24, 239–246 (2018) 10.1038/nm.4470.
2024 | John Hansen Research Grant (DKMS) |
| 2023 | Abstract Achievement Award (American Society of Hematology) |
| 2023 | Young Investigator Award, Annual Meeting of the German, Austrian and Swiss Societies for Hematology and Oncology |
| 2021 | Hans Jochem Kolb Award for Advances in Allogeneic Stem Cell |
| 2021-2023 | Walter-Benjamin Fellowship of the Deutsche Forschungsgemeinschaft |
| 2020 | ReForm A Fellowship for Young Investigators, University of Regensburg |
| 2019 | Regensburg Oncology Award (Comprehensive Cancer Center Regensburg) |
| 2018 | Jon J. van Rood Award (EBMT with E. Velardi and J. Tsai) |
| 2014 | Abstract Achievement Award (American Society of Hematology) |
| 2013-2014 | MD Fellowship, Boehringer Ingelheim Fonds |
| 2012-2017 | Scholar of the German National Academic Foundation (Studienstiftung des deutschen Volkes) |