title: Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment.
abstract: BACKGROUND
  While current treatment for acute myeloid leukemia is characterized by high response rates, patients' long-term outcome is still disappointing, due to frequent relapse and ineligibility of the often elderly patients for stem cell transplantation approaches. Considerable efforts have, thus, been made to incorporate immunotherapeutic approaches in the acute myeloid leukemia (AML) consolidation, with so far disappointing clinical benefit. The B7 family ligand programmed-death receptor-ligand 1 (PD-L1, B7-H1, CD274) has been recently described (with conflicting results) to be expressed on AML blast cells, and interaction with its receptor on T cells, programmed death receptor-1 (PD-1, CD279), has been shown to suppress T-cell functions and to allow survival of dormant AML cells in animal models.
  
  
  METHODS
  In this work, we analyzed freshly isolated myeloid precursor cells from healthy donors and from AML patients for PD-L1 expression with or without interferon-γ exposure at different time points during their treatment.
  
  
  RESULTS
  While without IFN exposure, only minor differences were observed, we found IFN-γ-induced PD-L1 expression most prominent after initial treatment and independent of treatment outcome.
  
  
  CONCLUSIONS
  Our observations support the recently suggested PD-L1-mediated adaptive immune resistance and argue for a targeting of the PD-L1/PD-1 pathway during the consolidation phase of AML treatment.
authors.affiliation: Department of Hematology and Medical Oncology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Krönig
authors.forename: Lukas
authors.initials: L
authors.lastname: Kremmler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.forename: Carsten
authors.initials: C
authors.lastname: Englert
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012008:Recurrence; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
keywords: IFN; PD-1; PD-L1; acute myeloid leukemia