- Research Project
Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections – CRC 1292
- Life Sciences
Cancer and chronic infections evade the immune system by manipulating host defense mechanisms. Immunotherapies, such as checkpoint inhibitors, have been developed to target these mechanisms. However, durable responses remain limited due to the complex immunosuppressive environment in tumors and chronically infected tissues.
The goal of the CRC 1292 is to identify and target convergent mechanisms underlying immune evasion and inefficient immunity in tumors and chronic infections. We aim to integrate disease-focused research with preclinical animal models and molecular systems immunology to dissect the pathophysiological processes underlying inefficient immunity.
Key mechanisms contributing to inefficient immunity include antigenic camouflage, cytokine and soluble mediator modulation, and signal transduction cascade manipulation. Therapies targeting these pathways, such as monoclonal antibodies and cytokine traps, aim to restore proper immune function.
We have made significant progress in deciphering the mechanisms of pH sensing in tissues and the role of coagulation proteases in regulating immune responses during viral infections. We have also investigated small molecules that affect signaling pathways, interfering with both the formation of metastasis and viral replication.
Our research has identified shared molecular programs in tumor Treg cells, normal tissue adjacent to tumor Treg cells, Treg cells present in infected tissues, and healthy tissue Treg cells in mice and humans. We have also observed that the microbiome is essential for the production of basal levels of Type I Interferons, which are central to the functional activation of innate immune cells and subsequent priming of adaptive immune responses.
Our findings have high potential for clinical translation and compatibility with existing immunotherapy regimens. Several clinical trials have been initiated based on these results. We will continue to analyze the mechanisms with the potential to be relevant in both tumors and chronic infections, with the aim of generating a detailed map of shared and disease-specific immune escape checkpoints.
In autumn 2025, the third funding period of the Collaborative Research Center 1292, which has been funded by the German Research Foundation (DFG) since 2018, was approved. The initiative is led by Johannes Gutenberg Uversity Mainz; experts from the RMU partner institutions Goethe University Frankfurt am Main and the Georg-Speyer-Haus are involved as project leaders.
