title: NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma.
abstract: Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is not typical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been poorly studied in patients with B-CLL/SLL. Here we report for the first time the NK cell phenotype and function in patients with B-CLL and SLL alongside their transcriptional profile. We show for the first time impaired B-CLL NK cell function in a xenograft model with reduced activating receptor expression including NKG2D, DNAM-1 and NCRs in-vitro. Importantly, we show these functional differences are associated with transcriptional downregulation of cytotoxic pathway genes, including activating receptors, adhesion molecules, cytotoxic molecules and intracellular signalling molecules, which remain intact in patients with SLL. In conclusion, NK cell function is markedly influenced by the anatomical site of the tumor in patients with B-CLL/SLL and lymphocytosis leads to marked impairment of NK cell activity. These observations have implications for treatment protocols which seek to preserve immune function by limiting the exposure of NK cells to tumor cells within the peripheral circulation.
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Parry
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Stevens
authors.affiliation: Institute of Cancer and Genomic Sciences, College of Medical and Dental Science, University of Birmingham, B15 2TT, UK.
authors.forename: Ceri
authors.initials: C
authors.lastname: Oldreive
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.
authors.forename: Bassier
authors.initials: B
authors.lastname: Zadran
authors.affiliation: Institute of Cancer and Genomic Sciences, College of Medical and Dental Science, University of Birmingham, B15 2TT, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: McSkeane
authors.affiliation: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Rudzki
authors.affiliation: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK.
authors.forename: Shankara
authors.initials: S
authors.lastname: Paneesha
authors.affiliation: Biomedical Services Unit, University of Birmingham, B15 2TT, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chadwick
authors.affiliation: Institute of Cancer and Genomic Sciences, College of Medical and Dental Science, University of Birmingham, B15 2TT, UK.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stankovic
authors.affiliation: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zuo
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Moss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D023041:Xenograft Model Antitumor Assays / Q000379:methods
keywords: NK cells; chronic lymphocytic leukaemia; immunomodulation; small lymphocytic lymphoma