INTEGRATED CLINICAL , HISTOPATOLOGICAL AND BIOMARKER SIGNATURES OF CALCINEURIN INHIBITOR-INDUCED IMMUNOMODULATION IN TRANSPLANT RECEPIENTS^ A SYSTEMATIC REVIEW-BASED RESEARCH PROPOSAL

Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, remain foundational in preventing allograft rejection in solid organ transplantation. However, their long-term use is associated with complex immunomodulatory effects that extend beyond T-cell suppression, influencing immune architecture, lymphoid organ morphology, and systemic inflammatory profiles. This proposal outlines a systematic, review-based research framework aimed at synthesizing current evidence on the clinical manifestations and histopathological alterations induced by CNIs, with a specific focus on immune system remodeling and biomarker discovery. By integrating data from clinical outcomes, tissue-level changes, and molecular biomarkers, this study seeks to identify mechanistic pathways linking CNI exposure to immune dysregulation, infection susceptibility, and graft outcomes. The findings are expected to inform precision immunosuppression strategies and guide future translational research.