Impact of Epstein Barr Virus Infection on Treatment Opportunities in Patients with Nasopharyngeal Cancer

SIMPLE SUMMARY: Epstein Barr virus (EBV) is often responsible for the onset of both solid and hematologic malignancies. In particular, it is implicated in the pathogenesis of nasopharyngeal carcinomas (NPCs). Some viral proteins produced during the latent phase of the virus itself in epithelial cells induce or promote carcinogenesis. These oncoproteins can be used as targets of various immunotherapy strategies. In the past, active or adoptive immunotherapy techniques have been employed. Recently however, the use of check-point inhibitors seems very promising. Some check-point inhibitors are already in use in clinical practice, others will soon receive regulatory approval. ABSTRACT: Chemical, physical, and infectious agents may induce carcinogenesis, and in the latter case, viruses are involved in most cases. The occurrence of virus-induced carcinogenesis is a complex process caused by an interaction across multiple genes, mainly depending by the type of the virus. Molecular mechanisms at the basis of viral carcinogenesis, mainly suggest the involvement of a dysregulation of the cell cycle. Among the virus-inducing carcinogenesis, Epstein Barr Virus (EBV) plays a major role in the development of both hematological and oncological malignancies and importantly, several lines of evidence demonstrated that nasopharyngeal carcinoma (NPC) is consistently associated with EBV infection. Cancerogenesis in NPC may be induced by the activation of different EBV “oncoproteins” which are produced during the so called “latency phase” of EBV in the host cells. Moreover, EBV presence in NPC does affect the tumor microenvironment (TME) leading to a strongly immunosuppressed status. Translational implications of the above-mentioned statements are that EBV-infected NPC cells can express proteins potentially recognized by immune cells in order to elicit a host immune response (tumor associated antigens). Three immunotherapeutic approaches have been implemented for the treatment of NPC including active, adoptive immunotherapy, and modulation of immune regulatory molecules by use of the so-called checkpoint inhibitors. In this review, we will highlight the role of EBV infection in NPC development and analyze its possible implications on therapy strategies.