{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:44:04Z","timestamp":1785404644216,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,10]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/038ja4880","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA189806"],"award-info":[{"award-number":["CA189806"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Terminally differentiated CD56\n                  <jats:sup>neg<\/jats:sup>\n                  CD16\n                  <jats:sup>pos<\/jats:sup>\n                  NK cells have been described after chronic viral and malaria infections, and in children diagnosed with Burkitt lymphoma (BL). Despite CD56\n                  <jats:sup>neg<\/jats:sup>\n                  NK cells appearing to be poor at direct cytotoxicity, they express high levels of cytotoxic granules (i.e. granzymes, perforin), activation markers, and Fc-\u03b3 receptors (CD32 and CD16) that are typically engaged in antibody-dependent cell cytotoxicity (ADCC). In addition, the abundance of CD56\n                  <jats:sup>neg<\/jats:sup>\n                  NK cells strongly correlates with IgG1 and IgG3 plasma levels, which are essential subclasses for ADCC. To determine whether CD56\n                  <jats:sup>neg<\/jats:sup>\n                  NK cells have superior ADCC capacity relative to CD56\n                  <jats:sup>dim<\/jats:sup>\n                  NK cells, we performed ADCC assays using effector cells from pediatric cancer patients and healthy children from malaria endemic regions of Kenya, targeting\n                  <jats:italic>in vitro<\/jats:italic>\n                  rituximab-treated commercial and newly established BL cell lines. We found that CD56\n                  <jats:sup>neg<\/jats:sup>\n                  NK cells were indeed capable of\n                  <jats:italic>in vitro<\/jats:italic>\n                  ADCC, showing a significant increase of CD107a-mediated degranulation in the presence of rituximab; however, they were not as efficient as CD56\n                  <jats:sup>dim<\/jats:sup>\n                  NK cells. Moreover, we found that the ADCC magnitude was significantly lower against EBV-Type 2 (EBV-T2) BL lines compared to EBV-Type 1 (EBV-T1). EBV-T2 tumor cell lines expressed significantly more lytic viral proteins than EBV-T1, making them more sensitive to direct cytotoxicity. Results from this study highlight the importance of assessing inter-patient variation in NK cell profiles in conjunction with ADCC sensitivity and EBV type within tumor cells when evaluating clinical outcomes for NK-mediated immunotherapies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>EBV type dictates NK cytotoxicity: EBV-T1 BL cells require rituximab for NK killing, while EBV-T2 BL cells are eliminated without antibody assistance, highlighting target-specific immune response to EBV-associated cancers.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.09.704808","type":"posted-content","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:15:22Z","timestamp":1770747322000},"source":"Crossref","is-referenced-by-count":0,"title":["EBV Type 1 versus Type 2: A determinant of NK cell anti-tumor activity in Burkitt lymphoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-5546","authenticated-orcid":false,"given":"Catherine S.","family":"Forconi","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Shumate","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Racenet","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester MA, 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Medicine, University of Massachusetts Chan Medical School, Worcester MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter O.","family":"Oluoch","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Chan Medical School, Worcester MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boaz","family":"Odwar","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Otieno","sequence":"additional","affiliation":[{"name":"Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry A.","family":"Vik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hematology\/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, 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