title: Programmed death-1 checkpoint blockade in acute myeloid leukemia.
abstract: BACKGROUND
  Immune checkpoints are regulatory pathways induced in activated T lymphocytes that regulate antigen responsiveness. These immune checkpoints are hijacked by tumors to promote dysfunction of anti-tumor effector cells and consequently of tumor escape from the host immune system.
  
  
  METHODS
  Programmed death-1/programmed death ligand (PD-1/PDL-1), a checkpoint pathway, has been extensively investigated in leukemia mouse models. Expression of PD-1 on the surface of activated immune cells and of its ligands, PD-L1 and PD-L2, on leukemic blasts has been documented. Clinical trials with PD-1 inhibitors in patients with hematological malignancies are ongoing with promising clinical responses.
  
  
  CONCLUSIONS
  Therapy of hematological cancers with antibodies blocking inhibitory receptors is expected to be highly clinically effective. Checkpoint inhibitory receptors and their ligands are co-expressed on hematopoietic cells found in the leukemic milieu. Several distinct immunological mechanisms are likely to be engaged by antibody-based checkpoint blockade. Co-expression of multiple inhibitory receptors on hematopoietic cells offers an opportunity for combining blocking antibodies to achieve more effective therapy. Up-regulation of receptor/ligand expression in the leukemic milieu may provide a blood marker predictive of response. Finally, chemotherapy-induced up-regulation of PD-1 on T cells after conventional leukemia therapy creates a solid rationale for application of checkpoint blockade as a follow-up therapy.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Division of Hematology/Oncology , 5150 Centre Avenue, Pittsburgh, PA 15232 , USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Sehgal
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Michael
authors.initials: M
authors.lastname: Boyiadzis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D018816:Genes, cdc / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor
keywords: acute myeloid leukemia; checkpoint inhibition; immunotherapy; programmed death-1