Roles of Inflammasomes in Epstein–Barr Virus-Associated Nasopharyngeal Cancer

SIMPLE SUMMARY: Inflammasomes play a key role in mediating innate immunity by regulating the processing and production of pro-inflammatory cytokines and eliminating foreign pathogens via pyroptosis. The expression of Epstein–Barr virus (EBV) viral antigens during EBV infection, a known causative agent of nasopharyngeal carcinoma (NPC), can trigger host’s antiviral immune response through activation of the inflammasomes and subsequent production of pro-inflammatory cytokines. This review explores the roles of inflammasomes during viral infection, the possible impact of inflammasomes on oncogenesis in EBV-associated NPC, and current developments in targeting inflammasomes for cancer treatment. With the contrasting roles of inflammasomes reported in different types of cancers, this paper aims to inspire further investigations into the exact role and mechanism of inflammasomes in EBV-associated NPC, as well as the therapeutic potentials of targeting inflammasomes in NPC. ABSTRACT: Epstein–Barr virus (EBV) infection is recognised as one of the causative agents in most nasopharyngeal carcinoma (NPC) cases. Expression of EBV viral antigens can induce host’s antiviral immune response by activating the inflammasomes to produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. These cytokines are known to be detrimental to a wide range of virus-infected cells, in which they can activate an inflammatory cell death program, called pyroptosis. However, aberrant inflammasome activation and production of its downstream cytokines lead to chronic inflammation that may contribute to various diseases, including NPC. In this review, we summarise the roles of inflammasomes during viral infection, how EBV evades inflammasome-mediated immune response, and progress into tumourigenesis. The contrasting roles of inflammasomes in cancer, as well as the current therapeutic approaches used in targeting inflammasomes, are also discussed in this review. While the inflammasomes appear to have dual roles in carcinogenesis, there are still many questions that remain unanswered. In particular, the exact molecular mechanism responsible for the regulation of the inflammasomes during carcinogenesis of EBV-associated NPC has not been explored thoroughly. Furthermore, the current practical application of inflammasome inhibitors is limited to specific tumour types, hence, further studies are warranted to discover the potential of targeting the inflammasomes for the treatment of NPC.