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EBV Type 1 versus Type 2: A determinant of NK cell anti-tumor activity in Burkitt lymphoma

Article scientifique 2026 Anglais

Résumé

Abstract Terminally differentiated CD56 neg CD16 pos NK cells have been described after chronic viral and malaria infections, and in children diagnosed with Burkitt lymphoma (BL). Despite CD56 neg NK cells appearing to be poor at direct cytotoxicity, they express high levels of cytotoxic granules (i.e. granzymes, perforin), activation markers, and Fc-γ receptors (CD32 and CD16) that are typically engaged in antibody-dependent cell cytotoxicity (ADCC). In addition, the abundance of CD56 neg NK cells strongly correlates with IgG1 and IgG3 plasma levels, which are essential subclasses for ADCC. To determine whether CD56 neg NK cells have superior ADCC capacity relative to CD56 dim NK cells, we performed ADCC assays using effector cells from pediatric cancer patients and healthy children from malaria endemic regions of Kenya, targeting in vitro rituximab-treated commercial and newly established BL cell lines. We found that CD56 neg NK cells were indeed capable of in vitro ADCC, showing a significant increase of CD107a-mediated degranulation in the presence of rituximab; however, they were not as efficient as CD56 dim 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. Significance 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.

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Forconi, C., Shumate, L., Racenet, Z., M’Bana, V., Oduor, C., Matta, A., Melo, J., Oluoch, P., Odwar, B., Otieno, J., Vik, T., N'juguna, F., Kinyua, A., Bailey, J., Münz, C., Moormann, A. (2026). EBV Type 1 versus Type 2: A determinant of NK cell anti-tumor activity in Burkitt lymphoma. https://doi.org/10.64898/2026.02.09.704808

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Auteur(s)

Catherine S. Forconi Lauren Shumate Zachary J. Racenet Viriato M’Bana Cliff I. Oduor Angela M. Matta Jeni Melo Peter O. Oluoch Boaz Odwar Juliana A. Otieno Terry A. Vik Festus N'juguna Ann W. Kinyua Jeffrey A. Bailey Christian Münz Ann M. Moormann

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