The impact of PD-1/PD-L1, CTLA-4, TIM-3 and LAG-3 immune checkpoint receptor expression in the development of acute graft versus host disease (aGVHD) and disease recurrence after allogeneic hematopoietic stem cell transplantation

The immune checkpoint receptors play a crucial role in managing the transplantation outcome including development of acute graft versus host disease (aGVHD) and disease recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is well established. This study aimed to investigate the expression of immune checkpoint receptors, including PD-1/PD-L1, CTLA-4, TIM-3, and LAG-3 in donors, as well as changes in their expression during the first 90 days (day 30 and day 90) post-HLA-matched allo-HSCT, concerning the development of aGVHD and disease relapse. Forty-one donor/recipient pairs were included in this study. The relative expression of immune checkpoint receptors was measured using the SYBR Green Real-Time PCR method. There was no significant relationship between the expression of PD-1/PD-L1, CTLA-4, TIM-3, and LAG-3 immune checkpoint receptors in donors and the occurrence of aGVHD and disease relapse. Additionally, alterations in the expression of these receptors during the initial 90 days post-transplantation did not correlate with aGVHD development. However, patients exhibiting elevated PD-L1 levels at day 90 had an increased risk of disease recurrence post-allo-HSCT (*P = 0.027). This study is the first to demonstrate that high PD-L1 expression in the peripheral blood at day 90 after allo-HSCT is associated with an increased rate of post-transplantation relapse.