title: The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment.
abstract: While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Gru
authors.affiliation: Division of Hematology, University of Colorado, Denver, CO, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Haverkos
authors.affiliation: Department of Pathology, Ohio State University, Columbus, OH, USA.|Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Freud
authors.affiliation: Division of Dermatology, Ohio State University, Columbus, OH, USA.|Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hastings
authors.affiliation: Department of Pathology, Ohio State University, Columbus, OH, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Nowacki
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas (INEN), Department of Pathology, Lima, Peru.
authors.forename: C
authors.initials: C
authors.lastname: Barrionuevo
authors.affiliation: Department of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Vigil
authors.affiliation: Department of Immunology and Microbiology, University of Colorado, Denver, CO, USA.
authors.forename: R
authors.initials: R
authors.lastname: Rochford
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Natkunam
authors.affiliation: Division of Hematology, and Comprehensive Cancer Center, The Ohio State University, B320 West 10th Avenue, Columbus, OH, 43210, USA.|Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Baiocchi
authors.affiliation: Division of Hematology, and Comprehensive Cancer Center, The Ohio State University, B320 West 10th Avenue, Columbus, OH, 43210, USA. pierluigi.porcu@osumc.edu.|Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA. pierluigi.porcu@osumc.edu.|Cutaneous Lymphoma Program, Ohio State University, Columbus, OH, USA. pierluigi.porcu@osumc.edu.
authors.forename: P
authors.initials: P
authors.lastname: Porcu
mesh_terms: D020031:Epstein-Barr Virus Infections / Q000821:virology*; D006801:Humans; D007694:Killer Cells, Natural / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000821:virology*; D011379:Prognosis
keywords: EBV; Latent; Lytic; Prognosis; T/NK-cell lymphoma