Over-expression of PD-1 Does Not Predict Leukemic Relapse after Allogeneic Stem Cell Transplantation

• Published in: Biology of blood and marrow transplantation 2019-02, Vol.25 (2), p.216-222
• Main Authors: Jain, Prachi, Tian, Xin, Cordes, Stefan, Chen, Jinguo, Cantilena, Caroline R., Bradley, Christian, Panjwani, Reema, Chinian, Fariba, Keyvanfar, Keyvan, Battiwalla, Minoo, Muranski, Pawel, Barrett, A. John, Ito, Sawa
• Format: Article
• Language: English
• Subjects: Adult; Allografts; Biomarker; Biomarkers, Tumor - immunology; Disease-Free Survival; Female; Follow-Up Studies; Gene Expression Regulation, Leukemic - immunology; Graft-versus-leukemia effect; Humans; Leukemia - immunology; Leukemia - mortality; Leukemia - pathology; Leukemia - therapy; Male; Middle Aged; Neoplasm Proteins - immunology; Post-transplant relapse; Programmed Cell Death 1 Receptor - immunology; Recurrence; Stem Cell Transplantation; Survival Rate
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.09.037

•PD-1 was overexpressed in T cells after allogeneic stem cell transplantation irrespective to subsequent relapse.•Helios+ regulatory T cells and CD8 EM cells emerged as independent predictors of relapse.•Single-cell analysis revealed overexpression of other exhaustion markers at relapse. Blockade of the T-cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematologic malignancy after allogeneic stem cell transplantation limits the success of this approach, and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its relationship with post-transplant relapse is poorly described. Because the donor immunity is activated by alloresponses, PD-1 expression may differ from nontransplanted individuals, and PD-1 blockade could risk graft-versus-host disease. Here we analyzed T-cell exhaustion marker kinetics and their relationship with leukemia relapse in 85 patients undergoing myeloablative T-cell-depleted HLA-matched stem cell transplantation. At a median follow-up of 3.5 years, 35 (44%) patients relapsed. PD-1 expression in CD4 and CD8 T cells was comparably elevated in relapsed and nonrelapsed cohorts. Helios+ regulatory T cells and CD8 effector memory cells at day 30 emerged as independent predictors of relapse. Although leukemia antigen-specific T cells did not overexpress PD-1, single-cell analysis revealed LAG3 and TIM3 overexpression at relapse. These findings indicate that PD-1 is an unreliable marker for leukemia-specific T-cell exhaustion in relapsing patients but implies other exhaustion markers and suppressor cells as relapse biomarkers.