Sensitizing Burkitt lymphoma to EBV-CTLs

Abstract

In this issue of Blood, Dalton et al show that epigenetic therapy with decitabine can upregulate immunogenic Epstein-Barr virus (EBV) antigens on Burkitt lymphoma (BL) that normally only express the less immunogenic antigen EBV nuclear antigen-1 (EBNA-1), rendering them sensitive to EBV-specific cells. The authors hypothesized that inducing expression of the more immunogenic latent viral antigens expressed in EBV type II and III latency tumors, such as posttransplant lymphoproliferative disease (PTLD), on EBV I latency tumors like BL, could improve the activity of virus-directed immunotherapies against these tumors.

There are 4 EBV latency states in B cells. Type III latency is the most immunogenic with expression of all of the latency-associated proteins that induce B-cell transformation and is seen in lymphomas that arise in individuals with profound immunosuppression such as PTLD. Type II latency tumors that include some cases of Hodgkin lymphoma and some NHLs express EBNA1, LMP1, and LMP2 and have intermediate immunogenicity. BL expresses type I latency with only EBNA1 expressed and is poorly susceptible to an EBV-CTL response. In type 0 latency, seen in normal memory B cells, no viral genes are expressed. Dalton et al show that incubation of type I latency lymphoma cells with decitabine can result in upregulation of the LMP1 and EBNA2 genes, making these cells more susceptible to EBV-CTLs. NK-T, natural killer T cell.