Oncotarget

Research Papers:

NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma

Helen M. Parry, Tom Stevens, Ceri Oldreive, Bassier Zadran, Tina McSkeane, Zbigniew Rudzki, Shankara Paneesha, Caroline Chadwick, Tatjana Stankovic, Guy Pratt, Jianmin Zuo, Paul Moss _

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Oncotarget. 2016; 7:68513-68526. https://doi.org/10.18632/oncotarget.12097

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Abstract

Helen M. Parry1, Tom Stevens1, Ceri Oldreive2, Bassier Zadran1, Tina McSkeane2, Zbigniew Rudzki3, Shankara Paneesha3, Caroline Chadwick4, Tatjana Stankovic2, Guy Pratt3, Jianmin Zuo1,*, Paul Moss1,*

1Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK

2Institute of Cancer and Genomic Sciences, College of Medical and Dental Science, University of Birmingham, B15 2TT, UK

3Department of Haematology, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK

4Biomedical Services Unit, University of Birmingham, B15 2TT, UK

*Co-senior authors

Correspondence to:

Jianmin Zuo, email: J.Zuo@bham.ac.uk

Paul Moss, email: P.Moss@bham.ac.uk

Keywords: NK cells, chronic lymphocytic leukaemia, small lymphocytic lymphoma, immunomodulation

Received: April 11, 2016     Accepted: September 12, 2016     Published: September 17, 2016

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.


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