Programmed Death 1 Expression on CD4⁺ T Cells Predicts Mortality after Allogeneic Stem Cell Transplantation

Area of Science:

• Immunology
• Transplantation Science
• Oncology

Background:

• Programmed death 1 (PD-1) is a key immune checkpoint receptor.
• Elevated PD-1 expression on T cells is associated with impaired immune responses in chronic infections and cancer.
• The role of PD-1 in allogeneic stem cell transplantation (SCT) outcomes requires further investigation.

Purpose of the Study:

• To investigate the expression of PD-1 on T cells post-allogeneic SCT.
• To determine the association between PD-1 expression levels and patient survival.
• To analyze PD-1 expression in different T cell subsets and transplant types.

Main Methods:

• Analysis of PD-1 expression and T cell maturation phenotype in 42 patients early after SCT (cord blood, matched unrelated donor, matched related donor).
• Flow cytometry was used to quantify PD-1 expression on CD4+ T cells and specific T cell subsets (central memory, effector memory).
• Statistical analysis was performed to compare PD-1 levels between survivors and nonsurvivors, and across different transplant types.

Main Results:

• PD-1 expression was significantly elevated on CD4+ T cells in all SCT types, with the highest levels in cord blood recipients.
• Nonsurvivors exhibited significantly higher PD-1 expression on CD4+ T cells compared to survivors (40.2% vs. 23.6%, P=.001).
• Elevated PD-1 was particularly pronounced on CD4+ T central memory and effector memory cells in nonsurvivors, especially in cord blood SCT.

Conclusions:

• Increased PD-1 expression on CD4+ T cells early after SCT is associated with higher mortality risk.
• Cord blood SCT recipients with high PD-1 expression show a particularly elevated risk of mortality.
• These findings suggest the PD-1 pathway plays a critical role in SCT outcomes and may represent a therapeutic target.