Over-expression of PD-1 does not predict leukemic relapse after allogeneic stem cell transplantation.
Biol Blood Marrow Transplant. 2018 Oct 04;:
Authors: Jain P, Tian X, Cordes S, Chen J, Cantilena CR, Bradley C, Panjwani R, Chinian F, Keyvanfar K, Battiwalla M, Muranski P, Barrett AJ, Ito S
Blockade of the T cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematological malignancy after allogeneic stem cell transplantation (allo-SCT) 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. Since the donor immunity is activated by allo-responses, PD-1 expression may differ from non-transplanted 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 SCT. 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 non-relapsed 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.
PMID: 30292745 [PubMed – as supplied by publisher]