期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 25, 期 2, 页码 216-222出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2018.09.037
关键词
Post-transplant relapse; Biomarker; Graft-versus-leukemia effect
资金
- Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZICAI001226] Funding Source: NIH RePORTER
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. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
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