title: Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.
abstract: Antibodies aimed at blocking the interaction between programmed cell death-1 (PD-1) and its ligands have shown impressive efficacy in a variety of malignancies and are generally well tolerated. Research has focused intensely on T cells and their interaction with cells within melanoma tumors, while relatively little is understood about the systems immunology of the cells in the blood during checkpoint inhibitor therapy. Longitudinal cytomic analysis using mass cytometry can characterize all the cells in a small sample of blood and has the potential to reveal key shifts in the cellular milieu occurring during treatment. We report a case of advanced melanoma in which mass cytometry detected abnormal myeloid cells resulting from myelodysplastic syndrome (MDS) in the blood following treatment with an anti-PD-1 agent. Myeloid blasts comprised <1% of peripheral blood mononuclear cells (PBMC) 1 month after the start of treatment. Six months after starting therapy, myeloid blasts comprised 5% of PBMCs, and a bone marrow biopsy confirmed refractory anemia with excess blasts-2 (RAEB-2). Longitudinal mass cytometry immunophenotyping comprehensively characterized blast phenotype evolution and revealed elevated PD-1 expression on the surface of nonblast myeloid cells. These findings highlight the clinical significance of cytomic monitoring, indicate that the myeloid compartment should be monitored during checkpoint inhibitor therapy, and emphasize the value of systems immunology in medicine. Cancer Immunol Res; 4(6); 474-80. ©2016 AACR.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.|Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Greenplate
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.|Laboratoire d'Hématologie, Pôle Cellules et Tissus, CHU, INSERM UMR 917, Rennes, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Savona
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.|Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: P Brent
authors.initials: PB
authors.lastname: Ferrell
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.|Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Irish
mesh_terms: D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab