Transplantation immunology: paradigm shift from systemic suppression to microenvironment remodeling and precision...

Area of Science:

• Transplant immunology
• Immunotherapy
• Precision medicine

Background:

• Organ transplantation is key for end-stage organ failure but faces challenges from allograft rejection.
• Current immunosuppression causes infections and malignancies, hindering long-term graft survival.

Purpose of the Study:

• To review the alloimmune response and explore novel therapeutic strategies.
• To outline a precision medicine framework for personalized immune management in transplantation.

Main Methods:

• Systematic review of the hierarchical network and regulatory mechanisms of the alloimmune response.
• Focus on four pioneering therapeutic strategies: engineered cellular therapies, targeted biologics, local microenvironment remodeling, and metabolic/epigenetic interventions.
• Integration of high-dimensional technologies (single-cell sequencing, epigenomics, metabolomics), biomarkers, and AI.

Main Results:

• Advances in high-dimensional technologies are shifting transplant immunology towards precision modulation.
• Four key therapeutic strategies show promise for targeted immune management.
• A precision medicine framework integrating novel technologies and AI can personalize immune management.

Conclusions:

• Transitioning from broad immunosuppression to precision modulation is crucial for improving long-term organ transplant outcomes.
• Future directions include xenotransplantation, spatial multi-omics, and addressing immune aging for enhanced graft survival.