Abstract
A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%–30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells’ role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment.
Highlights
Epstein-Barr Virus (EBV), known as human gammaherpesvirus 4 (HSV-4), is commonly spread through saliva and carried by a majority of the world’s population
Epithelial malignancies account for nearly 80% of all EBV-associated cancers, with Nasopharyngeal Carcinoma (NPC) being one of the most common EBV-associated epithelial cancers, which carries an annual prevalence of 78,100 diagnosed cases reported worldwide [7]
Refractory NPC patients have been treated with infusion of EBV-primed cytotoxic T lymphocytes (CTLs) with some success [5,23,24,25], validating the role of cell therapy in NPC
Summary
Epstein-Barr Virus (EBV), known as human gammaherpesvirus 4 (HSV-4), is commonly spread through saliva and carried by a majority of the world’s population. Refractory NPC patients have been treated with infusion of EBV-primed cytotoxic T lymphocytes (CTLs) with some success [5,23,24,25], validating the role of cell therapy in NPC The review of this treatment in NPC was reported in our previous publication [26]. Human Leukocyte Antigen (HLA) class I, a molecule required for priming and activation of CTLs, are common tumor evasion mechanisms among EBV-associated NPC [27,28,29] This loss of HLA class I molecules on NPC, presents an opportunity for Natural killer (NK) cells to kill these cancer cells, since NK cell-mediated cytotoxicity is not HLA dependent. Understanding the interactions between NK cells, EBV and NPC will aid in shaping novel therapeutic interventions in EBV-associated NPC
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