Whole-Body AI-Based Profiling of Nerve–Immune–Cancer Interactions in Immunotherapy Response

• Applicant: Professor Dr. Ali Ertürk
• Subject Area: Immunology ; Hematology, Oncology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577405586

Cancer metastases remain the leading cause of cancer-related deaths. While modern immunotherapies have transformed treatment for many patients, a large proportion of metastatic tumors remain resistant. A central, unresolved question is why some metastases respond to immunotherapy while others, even within the same patient, do not. Our project investigates a previously underappreciated factor in this process: the role of the nervous system. Emerging evidence suggests that bidirectional communication between nerves and the immune system shapes the tumor microenvironment, tumor growth and therapy response. We hypothesize that the spatial proximity of nerves to immune and cancer cells within micrometastases critically determines whether these lesions respond to or resist immunotherapy. To address this question, we will combine cutting-edge experimental and computational approaches. Using whole-body tissue clearing and light-sheet microscopy, we will visualize tiny metastases across the entire organism at single-cell resolution. Artificial intelligence-based pipelines will automatically quantify their number, location, innervation, and therapeutic antibody binding. In parallel, we will analyze the cellular architecture of the micrometastatic microenvironment with high-dimensional multiplexed immunofluorescence. Finally, we will functionally test whether blocking nerve-derived signals, for example with clinically approved beta-blockers or neuropeptide antagonists, can improve the efficacy of immune checkpoint inhibitors in preclinical models. This project will deliver the first comprehensive whole-body map of nerve–immune–cancer interactions in metastases. The results will shed light on fundamental mechanisms of immunotherapy resistance and identify novel therapeutic opportunities by targeting nerve–tumor communication. In the long term, our work could pave the way for more precise, site-specific treatments that take into account the local microenvironment of metastases.

• DFG Programme: Research Grants