Zippelius Lab
Research focus
Cancer develops within a complex ecosystem known as the tumor microenvironment (TME), where malignant cells continuously interact with immune, stromal, and vascular cells. These interactions profoundly influence disease evoluation and often establish conditions that suppress effective anti-tumor immunity.
Our laboratory investigates how the TME shapes immune cell behaviour, alters cellular function, and ultimately determines therapeutic outcome. We study the dynamic interactions between immune populations and their surrounding tissue environment to understand how immune responses are initiated, maintained, or disrupted during cancer progression.
Beyond individual cell populations, we are interested in the broader organization of tumors. We investigate how cellular composition, immune infiltration patterns, and tissue architecture influence therapeutic responses and determine whether tumors remain susceptible or resistant to immune attack.
By combining mechanistic studies in preclinical models that recapitulate human tumors with cutting-edge analyses of patient-derived samples and advanced model systems, we uncover the mechanisms that shape anti-tumor immunity and translate these insights into new therapeutic opportunities.
Questions that drive our research
Trefny et al., (Nat Comm. 2023)
What shuts down
T cells within tumors?
T cells are among the most powerful mediators of anti-tumor immunity. However, within tumors they often enter dysfunctional states characterized by impaired effector function, altered metabolism, and progressive exhaustion.
We investigate how chronic antigen exposure, suppressive signaling pathways, and metabolic stress reshape the biology of both CD8 and CD4 T cells. Through genetic screens, sophisticated mouse models, and analyses of patient samples, we seek to identify the molecular pathways that limit T-cell function and to develop strategies capable of restoring durable anti-tumor immunity.
Can NK cells succeed where
T cells fail?
Natural killer (NK) cells provide a complementary arm of immune defense through their ability to recognize and eliminate transformed cells independently of antigen-specific recognition.
Our work has contributed to establishing NK cells as promising therapeutic targets in cancer. We now investigate how distinct NK-cell populations emerge within tumors, how they adapt to the tumor microenvironment, and how their anti-tumor activity can be enhanced. By understanding the biology of intratumoral NK cells, we aim to develop therapeutic approaches that complement and extend current T-cell-based immunotherapies.
Serger et al., (Sci Immunol. 2026)
How does neutrohil plasticity shape anti-tumor immunity?
Neutrophils are increasingly recognized as highly dynamic immune cells whose functions are determined by local and systemic inflammatory signals.
We investigate how neutrophils acquire distinct activation states within tumors and how these states influence immune responses, disease progression, and therapeutic outcome. By defining the molecular programs that govern neutrophil plasticity, we aim to understand how innate immunity contributes to cancer control and identify new opportunities for therapeutic intervention.
How can the tumor microenvironment be reprogrammed?
The effectiveness of immunotherapy is influenced not only by immune cells themselves, but also by the broader tissue context in which they operate.
Our research seeks to understand how immune-excluded or immunologically silent tumors can be converted into inflamed, therapy-responsive environments. Through collaborations with academic and industrial partners, we investigate novel strategies that reshape immune and stromal interactions within tumors. By identifying the determinants of successful tumor reprogramming, we aim to develop rational therapeutic combinations that improve patient outcomes.
Kirchhammer et al., (Sci Transl Med. 2022)
How can we bring discoveries
closer to patients?
Modeling human tumor immunity
A central challenge in cancer research is translating biological discoveries into clinical benefit. To bridge this gap, we employ advanced ex vivo platforms that preserve the cellular diversity, architecture, and functional complexity of human tumors. Using patient-derived tumor fragments, organoid-based systems, and other translational models, we directly evaluate novel therapeutic concepts within intact human tumor ecosystems.
These platforms allow us to study mechanisms of action, capture patient-to-patient variability, and generate insights that are both biologically robust and clinically relevant. By integrating these systems into our discovery pipeline, we accelerate the translation of promising immunotherapeutic strategies toward clinical testing.
From discovery to clinical translation
Translation is a defining component of our research. Through close collaborations with clinicians, academic investigators, and biotechnology partners, we rapidly advance promising discoveries toward therapeutic development and early-phase clinical evaluation.
Our ultimate goal is straightforward: to understand how the immune system can be mobilized more effectively against cancer and to translate this knowledge into better treatment options for patients.
Collaborators and support
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