Personalizing immunosuppression in liver transplantation via integration of spatial immunology

• Applicant: Dr. Christian Niehaus
• Subject Area: Gastroenterology ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575743435

Liver transplantation has significantly improved outcomes and quality of life for patients with organ failure, yet long-term success remains challenged by the need for lifelong immunosuppressive (IS) therapy. While IS therapy is essential to prevent rejection, it also increases the risk of complications such as nephrotoxicity, diabetes, infections, and malignancies. Current IS management follows a generalized medicine approach where decision-making relies on conventional histopathological and clinical assessments, which lack detailed immune profiling and the possibility for personalized medicine. Thus, there is a need for improved diagnostics that can identify immune signatures predictive of graft stability or rejection to enable optimized IS adjustments. This project aims to improve long-term graft survival and IS management in liver transplantation by integrating spatial immune profiling into clinical transplant research. We hypothesize that turnover of immune cells in transplanted organs follows a predictable pattern. This pattern involves the gradual replacement of donor-derived immune cells by recipient-derived lymphocytes and monocytes. Understanding this process of spatial reconstruction is essential for identifying mechanisms of graft tolerance and rejection risk. We further hypothesize that subclinical rejection is driven by spatially distinct immune interactions that are not captured by conventional histopathology. Therefore, the first aim focuses on analyzing the spatial reconstruction over time, including definition of origin and turnover of immune cells in transplanted liver organs using flow cytometry, single-cell RNA sequencing, and ultra-deep spatial proteomics (MACSima). This will provide basic immunological insights into immune repopulation dynamics in liver transplantation. The second aim is to apply a retrospective-prospective study design to a large liver transplantation cohort in order to identify spatial immune signatures that are predictive of subclinical rejection and IS response. This will be achieved by leveraging paired biopsies and clinical data in order to establish biomarkers that could inform future IS tapering strategies. Findings from the proposed research project will lay the foundation for future randomized clinical trials evaluating biomarker-driven IS management, ultimately advancing precision medicine in transplantation and reducing IS-related complications while preserving graft function.

• DFG Programme: WBP Fellowship
• International Connection: Sweden
• Host: Professor Niklas Björkström, Ph.D.