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    Poorly cytotoxic terminally differentiated CD56(neg)CD16(pos) NK cells accumulate in Kenyan children with Burkitt lymphomas

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    Authors
    Forconi, Catherine
    Cosgrove, Cormac P.
    Saikumar-Lakshmi, Pryia
    Nixon, Christina E.
    Foley, Joslyn
    Ong'echa, John Michael
    Otieno, Juliana A.
    Alter, Galit
    Munz, Christian
    Moormann, Ann M.
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2018-05-22
    Keywords
    endemic Burkitt lymphoma
    Natural killer (NK) cells
    Hematology
    Hemic and Lymphatic Diseases
    Immunology and Infectious Disease
    Neoplasms
    Oncology
    Virus Diseases
    
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965049/
    Abstract
    Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya. We defined 5 subsets based on CD56 and CD16 expression, including CD56(neg)CD16(pos) We found that licensed and terminally differentiated perforin-expressing CD56(neg)CD16(pos) NK cells accumulated in eBL children, particularly in those with high EBV loads (45.2%) compared with healthy children without (6.07%) or with (13.5%) malaria exposure (P = .0007 and .002, respectively). This progressive shift in NK cell proportions was concomitant with fewer CD56(dim)CD16(pos) cells. Despite high MIP-1beta expression, CD56(neg)CD16(pos) NK cells had diminished cytotoxicity, with lower expression of activation markers NKp46, NKp30, and CD160 and the absence of TNF-alpha. Of note, the accumulation of poorly cytotoxic CD56(neg)CD16(pos) NK cells resolved in long-term eBL survivors. Our study demonstrates impaired NK cell-mediated immunosurveillance in eBL patients but with the potential to restore a protective NK cell repertoire after cancer treatment. Characterizing NK cell dysfunction during coinfections with malaria and EBV has important implications for designing immunotherapies to improve outcomes for children diagnosed with eBL.
    Source

    Blood Adv. 2018 May 22;2(10):1101-1114. doi: 10.1182/bloodadvances.2017015404. Link to article on publisher's site

    DOI
    10.1182/bloodadvances.2017015404
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/40685
    PubMed ID
    29764843
    Related Resources

    Link to Article in PubMed

    Rights
    © Blood Advances Online by the American Society of Hematology. Publisher PDF posted as allowed by the publisher's author rights policy at http://www.bloodadvances.org/page/authors/copyright-information.
    ae974a485f413a2113503eed53cd6c53
    10.1182/bloodadvances.2017015404
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