Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment

• Published in: European journal of haematology 2014-03, Vol.92 (3), p.195-203
• Main Authors: Krönig, Holger, Kremmler, Lukas, Haller, Bernhard, Englert, Carsten, Peschel, Christian, Andreesen, Reinhard, Blank, Christian U.
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; Adult; Aged; B7-H1 Antigen - metabolism; Cohort Studies; Female; Flow Cytometry; Gene Expression Regulation, Leukemic; Humans; IFN; Immunotherapy; Inflammation; Interferon-gamma - pharmacology; Leukemia, Myeloid, Acute - metabolism; Male; Middle Aged; PD-1; PD-L1; Programmed Cell Death 1 Receptor - metabolism; Recurrence; Signal Transduction; Stem Cell Transplantation; T-Lymphocytes - cytology; Treatment Outcome
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12228

Introduction 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. Design and 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.