Journal
JOURNAL OF MEDICAL VIROLOGY
Volume 95, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/jmv.27840
Keywords
CD27; CTLA-4; Epstein-Barr virus; Kaposi sarcoma-associated herpesvirus; PD-1
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This review discusses the role of costimulatory and coinhibitory receptors in EBV and KSHV-associated diseases, revealing the specificities of these receptors in tumor virus immunity, and emphasizing the importance of monitoring EBV and KSHV-specific immune control during immune checkpoint inhibition to prevent adverse events.
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are two persistent oncogenic gamma-herpesviruses with an exclusive tropism for humans. They cause cancers of lymphocyte, epithelial and endothelial cell origin, such as Burkitt's and Hodgkin's lymphoma, primary effusion lymphoma, nasopharyngeal carcinoma, and Kaposi sarcoma. Mutations in immune-related genes but also adverse events during immune checkpoint inhibition in cancer patients have revealed molecular requirements for immune control of EBV and KSHV. These include costimulatory and coinhibitory receptors on T cells that are currently explored or already therapeutically targeted in tumor patients. This review discusses these co-receptors and their influence on EBV- and KSHV-associated diseases. The respective studies reveal surprising specificities of some of these receptors for immunity to these tumor viruses, benefits of their blockade for some but not other virus-associated diseases, and that EBV- and KSHV-specific immune control should be monitored during immune checkpoint inhibition to prevent adverse events that might be associated with their reactivation during treatment.
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