Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.

Greenplate AR, Johnson DB, Roussel M, Savona MR, Sosman JA, Puzanov I, Ferrell PB, Irish JM
Cancer Immunol Res. 2016 4 (6): 474-480

PMID: 26966176 · PMCID: PMC4891280 · DOI:10.1158/2326-6066.CIR-15-0213

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.

©2016 American Association for Cancer Research.

MeSH Terms (13)

Aged Anemia, Refractory, with Excess of Blasts Antibodies, Monoclonal, Humanized Antineoplastic Agents Disease Progression Female Flow Cytometry Follow-Up Studies Humans Immunophenotyping Melanoma Myelodysplastic Syndromes Programmed Cell Death 1 Receptor

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