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Poorly cytotoxic terminally differentiated CD56(neg)CD16(pos) NK cells accumulate in Kenyan children with Burkitt lymphomas
Open Access Articles
  • Catherine Forconi, University of Massachusetts Medical School
  • Cormac P. Cosgrove, Ragon Institute of MGH, MIT and Harvard
  • Pryia Saikumar-Lakshmi, University of Massachusetts Medical School
  • Christina E. Nixon, Brown University
  • Joslyn Foley, University of Massachusetts Medical School
  • John Michael Ong'echa, Kenya Medical Research Institute
  • Juliana A. Otieno, University of Zurich, Switzerland
  • Galit Alter, Ragon Institute of MGH, MIT and Harvard
  • Christian Munz, University of Zurich, Switzerland
  • Ann M. Moormann, University of Massachusetts Medical School
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
5-22-2018
Document Type
Article
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

Related Resources

Link to Article in PubMed

PubMed ID
29764843
Citation Information
Catherine Forconi, Cormac P. Cosgrove, Pryia Saikumar-Lakshmi, Christina E. Nixon, et al.. "Poorly cytotoxic terminally differentiated CD56(neg)CD16(pos) NK cells accumulate in Kenyan children with Burkitt lymphomas" Vol. 2 Iss. 10 (2018) ISSN: 2473-9529 (Linking)
Available at: http://works.bepress.com/ann_moormann/72/