title: Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts.
abstract: Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts.
authors.affiliation: Institute of Cancer, Centre for Medical Oncology, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Rifca
authors.initials: R
authors.lastname: Le Dieu
authors.forename: David C
authors.initials: DC
authors.lastname: Taussig
authors.forename: Alan G
authors.initials: AG
authors.lastname: Ramsay
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Faridah
authors.initials: F
authors.lastname: Miraki-Moud
authors.forename: Rewas
authors.initials: R
authors.lastname: Fatah
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Lee
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex; D018955:CD36 Antigens; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D005838:Genotype; D006801:Humans; D054992:Immunological Synapses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D017252:CD3 Complex; D018955:CD36 Antigens