AUTHOR=Shindiapina Polina , Ahmed Elshafa H. , Mozhenkova Anna , Abebe Tamrat , Baiocchi Robert A. 

TITLE=Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01723

DOI=10.3389/fonc.2020.01723

ISSN=2234-943X

ABSTRACT=Epstein-Bar virus (EBV) is associated with increased risk of lymphoproliferative disease (LPD), including AIDS-defining lymphomas such as Burkitt’s lymphoma and other non-Hodgkin lymphomas, as well as HIV-related Hodgkin lymphoma (HL).  The prevalence of EBV in HL and non-Hodgkin lymphomas is elevated in HIV-positive individuals compared with the general population.  Rates of incidence of AIDS-defining cancers in HIV-infected individuals have been declining since initiation of combination anti-retroviral therapy (cART) use in 1996.  However, HIV-infected persons remain at an increased risk of cancers related to infections with oncogenic viruses.  Proposed pathogenic mechanisms of HIV-related cancers include decreased immune surveillance, decreased ability to suppress infection-related oncogenic processes and a state of chronic inflammation marked by alteration of the cytokine profile and expanded numbers of cytotoxic T lymphocytes, with down-regulated co-stimulatory molecules and increased expression of markers of senescence in the setting of treated HIV infection.  
In this review we discuss the cooperation of EBV-infected B cell- and environment-associated factors that may contribute to EBV-related lymphomagenesis in HIV-infected individuals. Environment-derived lymphomagenic factors include impaired host adaptive and innate immune surveillance, cytokine dysregulation and a pro-inflammatory state observed in the setting of chronic, cART-treated HIV infection.  B cell factors include distinctive EBV latency patterns and host protein expression in HIV-associated LPD, as well as B cell-stimulating factors derived from HIV infection.  We review the future directions for expanding therapeutic approaches in targeting the viral and immune components of EBV LPD pathogenesis.