UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

5-22-2018

Document Type

Article

Disciplines

Hematology | Hemic and Lymphatic Diseases | Immunology and Infectious Disease | Neoplasms | Oncology | Virus Diseases

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.

Keywords

endemic Burkitt lymphoma, Natural killer (NK) cells

Rights and Permissions

© 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.

DOI of Published Version

10.1182/bloodadvances.2017015404

Source

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

Journal/Book/Conference Title

Blood advances

Related Resources

Link to Article in PubMed

PubMed ID

29764843

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