Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

The Translational Cancer Immunotherapy Lab investigates how the tumor immune microenvironment drives cancer progression, therapy resistance, and relapse. We use systems immunology and computational biology approaches with single-cell and spatial technologies to map immune–cancer interactions at high resolution These insights are tested in advanced functional models, including genetically engineered mouse models. Through this integrative approach, we aim to translate mechanistic discoveries into innovative and personalized cancer immunotherapies. Through this integrative approach, we aim to translate mechanistic discoveries into innovative and personalized cancer immunotherapies.

Our research is driven by a dynamic, interdisciplinary team of clinician scientists, molecular biologists, and computational scientists. Together, we bring complementary expertise that bridges fundamental discovery and clinical application.

Decoding the Tumor Microenvironment

Our research begins with a central question: how do immune and cancer cells communicate within the tumor microenvironment to shape disease progression? We map these communication networks to uncover how immunosuppressive subsets, such as regulatory T cells (Wertheimer et al., Nature Immunology 2024), together with cytokine-driven signaling pathways, create niches that protect tumors and limit anti-tumor immunity. By integrating single-cell and spatial technologies with functional experiments in advanced models, we dissect these interactions at high resolution.

Building on these insights, we aim to turn communication networks into therapeutic entry points—identifying and targeting the mechanisms that underlie immune evasion in order to enhance the efficacy of cancer immunotherapies.

As a complementary line of research, we apply the same systems immunology methodologies to investigate toxicity in the context of cancer immunotherapy, mapping maladaptive communication patterns that drive adverse immune reactions. This dual perspective—on both tumor progression and treatment-associated toxicity—enables us to develop strategies that not only strengthen anti-tumor responses but also improve safety.

Relapse After Allogeneic Hematopoietic Cell Transplantation (allo-HCT)

A central focus of our research is relapse after allo-HCT, one of the major barriers to cure in hematologic malignancies. We apply systems-level profiling and functional models to dissect how residual cancer cells evade immune surveillance and resist graft-versus-leukemia effects. Our goal is to uncover mechanisms that can guide novel strategies for preventing and treating relapse.

Towards Personalized Immunotherapies

We integrate computational modeling and AI-driven analysis with translational studies to uncover determinants of therapy response, resistance, and relapse across multiple immunotherapy platforms, including CAR-T cells, immune checkpoint blockade, and allo-HCT. By identifying predictive biomarkers and targetable pathways, we aim to develop personalized immunotherapies that are both more effective and more durable.

Head of Wertheimer Laboratory

Principal Investigator

Dr. Tobias Wertheimer

  tobias.wertheimer@uniklinik-freiburg.de

Zentrum Translationale Zellforschung (ZTZ)

Breisacher Str. 115
D- 79106 Freiburg