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dc.contributor.authorHughes, A.-
dc.contributor.authorClarson, J.-
dc.contributor.authorTang, C.-
dc.contributor.authorVidovic, L.-
dc.contributor.authorWhite, D.-
dc.contributor.authorHughes, T.-
dc.contributor.authorYong, A.-
dc.identifier.citationBlood, 2017; 129(9):1166-1176-
dc.description.abstractImmunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n = 8), MMR (BCR-ABL1 ≤0.1%, n = 20), molecular response4.5 (MR4.5, BCR-ABL1 ≤0.0032%, n = 16), and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n = 13). Aberrant immune-inhibitory responses (myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and programmed death-1 (PD-1) inhibitory molecule expression on CD4+/CD8+ T cells were increased in CML patients at diagnosis. Consequent quantitative and functional defects of innate effector natural killer (NK) cells and cytotoxic T-lymphocyte responses to leukemia-associated antigens WT1, BMI-1, PR3, and PRAME were observed at diagnosis. Treg and PD-1+CD4+/CD8+ T cells persisted in pre-MMR CML patients on TKI. Patients in MMR and MR4.5 had a more mature, cytolytic CD57+CD62L- NK cell phenotype, consistent with restoration of NK cell activating and inhibitory receptor repertoire to normal healthy donor levels. Immune responses were retained in TFR patients off-therapy, suggesting the restored immune control observed in MMR and MR4.5 is not an entirely TKI-mediated effect. Maximal restoration of immune responses occurred only in MR4.5, as demonstrated by increased NK cell and effector T-cell cytolytic function, reduced T-cell PD-1 expression and reduced numbers of monocytic MDSCs.-
dc.description.statementofresponsibilityAmy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L. White, Timothy P. Hughes and Agnes S. M. Yong-
dc.publisherAmerican Society of Hematology-
dc.rights© 2017 by The American Society of Hematology-
dc.subjectKiller Cells, Natural-
dc.subjectCD4-Positive T-Lymphocytes-
dc.subjectCD8-Positive T-Lymphocytes-
dc.subjectAntineoplastic Agents-
dc.subjectProtein Kinase Inhibitors-
dc.subjectRemission Induction-
dc.subjectFlow Cytometry-
dc.subjectDrug Resistance, Neoplasm-
dc.subjectAged, 80 and over-
dc.subjectMiddle Aged-
dc.subjectLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subjectEnzyme-Linked Immunospot Assay-
dc.subjectProgrammed Cell Death 1 Receptor-
dc.subjectImatinib Mesylate-
dc.subjectMyeloid-Derived Suppressor Cells-
dc.titleCML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors-
dc.typeJournal article-
dc.identifier.orcidWhite, D. [0000-0003-4844-333X]-
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]-
dc.identifier.orcidYong, A. [0000-0001-9452-1533]-
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