title: Programmed cell death-1 pathway inhibition in myeloid malignancies: implications for myeloproliferative neoplasms.
abstract: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification. Immune checkpoint inhibition, in particular along the programmed cell death protein 1 (PD-1)/B7-H1 (PD-L1) axis, is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies. Seminal studies suggest that the pro-inflammatory microenvironment of MyMs can suppress T lymphocyte-mediated immunity via PD-1 signaling and that response to mainstay epigenetic therapies for MyMs may be governed by PD-1 gene regulation. Although the role of PD-1 signaling in MPN pathogenesis and progression is as yet unclear, research in MPN patients has revealed expansion of myeloid-derived suppressor cells (MDSCs), which may effect host immune tolerance of tumor via temporally and spatially specific activation of PD-1/PD-L1 signaling. The current understanding of immune dysfunction in MPNs and analogous MyMs offers a compelling rationale to study PD-1/PD-L1 inhibition in patients as a novel treatment option.
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Choi
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tremblay
authors.affiliation: Myeloproliferative Disorders Program, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1079, New York, NY, 10029, USA.
authors.forename: C
authors.initials: C
authors.lastname: Iancu-Rubin
authors.affiliation: Myeloproliferative Disorders Program, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1079, New York, NY, 10029, USA. john.mascarenhas@mssm.edu.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-8400-0483
authors.initials: J
authors.lastname: Mascarenhas
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Myelofibrosis; Myeloid malignancy; Programmed cell death pathway