Abstract Background Acute cellular rejection (ACR) remains a major obstacle to maintaining long-term graft function after heart transplantation. The programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) immune checkpoint pathway is a critical regulator of peripheral immune tolerance; however, its clinical and prognostic significance in human cardiac allografts has not been clearly established. This study evaluated the expression of PD-1 and PD-L1 and their association with immune cell infiltration, rejection grade, and post-transplant survival in heart transplant recipients. Methods Endomyocardial biopsy samples from 78 patients who underwent heart transplantation were analyzed by immunohistochemistry for PD-L1, PD-1, cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8). The expression levels of PD-L1 and the numbers of PD-1-positive, CD4-positive, and CD8-positive lymphocytes per high-power field were quantified and correlated with clinicopathological variables, ACR severity, and clinical outcomes including post-transplant survival. Results Allografts with high-grade ACR (International Society for Heart and Lung Transplantation grades 2R-3R) showed significantly higher PD-L1 expression than those without ACR (62.5% vs. 16.1%, P 0.001). PD-L1 expression correlated positively with PD-1-positive, CD4-positive, and CD8-positive lymphocyte infiltration (P = 0.390, 0.025, and 0.059, respectively). Univariate survival analysis demonstrated that the PD-1/PD-L1 immune status was associated with prognosis. Patients with higher PD-1-positive lymphocyte infiltration (≥1.0 cells per high-power field) had poorer overall survival than those with lower PD-1 expression (1.0, P = 0.086). A similar trend was observed for post-transplant survival (P = 0.183). Stratification by CD4-positive cell density showed shorter survival in patients with CD4 ≥ 90 compared with CD4 90 (P = 0.052). Notably, concurrent high PD-1 (≥1) and CD4 (≥90) infiltration was significantly associated with inferior post-transplant survival (χ² = 4.293, P = 0.038). Conclusions Activation of the PD-1/PD-L1 pathway reflects both immune regulatory engagement and sustained alloimmune stress that adversely affects graft survival. Combined PD-1 and CD4 lymphocytic infiltration identifies recipients at higher risk for poor post-transplant outcomes. These findings position the PD-1/PD-L1 axis as a dual-function biomarker—indicating immune modulation and prognostic vulnerability—and support its potential utility for post-transplant risk stratification and individualized immunotherapy. This abstract is funded by: None
Yim et al. (Fri,) studied this question.