Increased Expression Of Immune Checkpoint Programmed Cell Death Protein-1 (Pd-1) On T Cell Subsets Of Bone Marrow Aspirates In Patients Withb-Lymphoblasticleukemia, Especially In Relapse And At Diagnosis

Background We analyzed expression profiles of immune checkpoint receptors on T cell subsets and ligands on leukemic blasts in patients with B-lymphoblastic leukemia (B-ALL). Methods Total 149 bone marrow (BM) samples obtained from 65 B-ALL patients with four different clinical status (41 at diagnosis, 54 in complete remission [CR], 34 in persistence, and 20 in relapse), and 32 BM control samples were prospectively enrolled. Expression of immune checkpoint receptor (programmed cell death protein-1 [PD-1]) on T cell subsets and ligands (PD-L1, PD-L2) on leukemic blasts was evaluated by flow cytometry, and was compared between patient subgroups. Results Relapsed patients demonstrated highest PD-1 expression proportion and intensity on CD3(+)CD4(+)T cells with statistical significance when compared to patients in persistence/CR/BM controls (p= .027/<.001/<.001 and .012/.001/<.001, respectively). Newly diagnosed patients showed significantly lower PD-1 expression proportion on CD3(+)CD4(+)T cells than relapsed patients (p < .001), but their intensity was not significantly different. Relapsed patients showed significantly higher PD-1 expression proportion and intensity on CD3(+)CD8(+)T cells than patients in CR/BM controls (p= .022/.045 and .049/.005, respectively), but PD-1 expression status on them were not significantly different between relapsed and newly diagnosed patients. PD-L1/L2 expression on leukemic blasts was not significantly different between patient subgroups. Conclusions In BM aspirates from B-ALL patients, PD-1 expression on T-cell subsets is increased at diagnosis, and to a greater extent, at relapse. These data suggest the potential usefulness of PD-1 blockade in the treatment of B-ALL, particularly at relapse.