Facts and Hopes in the Relationship of EBV with Cancer Immunity and Immunotherapy

Epstein-Barr virus (EBV), the first identified human tumor virus, infects and takes up residency in almost every human. However, EBV genome-positive tumors arise in only a tiny minority of infected people, presumably when the viruscarrying tumor cells are able to evade immune surveillance. Traditional views regard viral antigens as the principal targets of host immune surveillance against virus-infected cells. However, recent findings indicate that EBV-infected/-transformed B cells elicit both cytotoxic CD8 and CD4 T-cell responses against a wide range of overexpressed cellular antigens known to function as tumor-associated antigens (TAA), in addition to various EBV-encoded antigens. This not only broadens the ways by which the immune system controls EBV infection and prevents it from causing cancers, but also potentially extends immune protection toward EBV-unrelated cancers by targeting shared TAAs. The goal of this review is to incorporate these new findings with literature data and discuss future directions for improved understanding of EBV-induced antitumor immunity, as well as the hopes for rational immune strategies for cancer prevention and therapy.