Show simple item record

dc.contributor.authorForconi, Catherine S
dc.contributor.authorCosgrove, Cormac P.
dc.contributor.authorSaikumar-Lakshmi, Pryia
dc.contributor.authorNixon, Christina E.
dc.contributor.authorFoley, Joslyn
dc.contributor.authorOng'echa, John Michael
dc.contributor.authorOtieno, Juliana A.
dc.contributor.authorAlter, Galit
dc.contributor.authorMunz, Christian
dc.contributor.authorMoormann, Ann M.
dc.date2022-08-11T08:09:50.000
dc.date.accessioned2022-08-23T16:45:27Z
dc.date.available2022-08-23T16:45:27Z
dc.date.issued2018-05-22
dc.date.submitted2018-07-27
dc.identifier.citation<p>Blood Adv. 2018 May 22;2(10):1101-1114. doi: 10.1182/bloodadvances.2017015404. <a href="https://doi.org/10.1182/bloodadvances.2017015404">Link to article on publisher's site</a></p>
dc.identifier.issn2473-9529 (Linking)
dc.identifier.doi10.1182/bloodadvances.2017015404
dc.identifier.pmid29764843
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40685
dc.description.abstractNatural 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29764843&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965049/
dc.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.
dc.subjectendemic Burkitt lymphoma
dc.subjectNatural killer (NK) cells
dc.subjectHematology
dc.subjectHemic and Lymphatic Diseases
dc.subjectImmunology and Infectious Disease
dc.subjectNeoplasms
dc.subjectOncology
dc.subjectVirus Diseases
dc.titlePoorly cytotoxic terminally differentiated CD56(neg)CD16(pos) NK cells accumulate in Kenyan children with Burkitt lymphomas
dc.typeJournal Article
dc.source.journaltitleBlood advances
dc.source.volume2
dc.source.issue10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4498&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3487
dc.identifier.contextkey12556169
refterms.dateFOA2022-08-23T16:45:27Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3487
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages1101-1114


Files in this item

Thumbnail
Name:
1101.full.pdf
Size:
1.711Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record