%0 Journal Article %1 10.1182/blood.2019004126 %A Dalton, Tanner %A Doubrovina, Ekaterina %A Pankov, Dmitry %A Reynolds, Raymond Cullen, III %A Scholze, Hanna %A Selvakumar, Annamalai %A Vizconde, Teresa %A Savalia, Bhumesh %A Dyomin, Vadim %A Weigel, Christoph %A Oakes, Christopher C. %A Alonso, Alicia %A Elemento, Olivier %A Pan, Heng %A Phillip, Jude M %A O'Reilly, Richard J %A Gewurz, Benjamin E %A Cesarman, Ethel %A Giulino-Roth, Lisa %D 2020 %J Blood %K b-cell epstein-barr lmp1 myown virus %R 10.1182/blood.2019004126 %T Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to viral directed immunotherapy %U https://doi.org/10.1182/blood.2019004126 %X Despite advances in T-cell immunotherapy against EBV-infected lymphomas that express the full EBV latency III program, a critical barrier has been that most EBV+ lymphomas express the latency I program, in which the single Epstein-Barr nuclear antigen (EBNA1) is produced. EBNA1 is poorly immunogenic, enabling tumors to evade immune responses. Using a high-throughput screen we identified decitabine as a potent inducer of immunogenic EBV antigens including LMP1, EBNA2 and EBNA3C. Induction occurs at low doses and persists after removal of decitabine. Decitabine treatment of latency I EBV+ Burkitt lymphoma sensitized cells to lysis by EBV-specific cytotoxic T-cells (EBV-CTLs). In latency I Burkitt lymphoma xenografts, decitabine followed by EBV-CTLs results in T-cell homing to tumors and inhibition of tumor growth. Collectively, these results identify key epigenetic factors required for latency restriction and highlight a novel therapeutic approach to sensitize EBV+ lymphomas to immunotherapy.

@article{10.1182/blood.2019004126, abstract = {{Despite advances in T-cell immunotherapy against EBV-infected lymphomas that express the full EBV latency III program, a critical barrier has been that most EBV+ lymphomas express the latency I program, in which the single Epstein-Barr nuclear antigen (EBNA1) is produced. EBNA1 is poorly immunogenic, enabling tumors to evade immune responses. Using a high-throughput screen we identified decitabine as a potent inducer of immunogenic EBV antigens including LMP1, EBNA2 and EBNA3C. Induction occurs at low doses and persists after removal of decitabine. Decitabine treatment of latency I EBV+ Burkitt lymphoma sensitized cells to lysis by EBV-specific cytotoxic T-cells (EBV-CTLs). In latency I Burkitt lymphoma xenografts, decitabine followed by EBV-CTLs results in T-cell homing to tumors and inhibition of tumor growth. Collectively, these results identify key epigenetic factors required for latency restriction and highlight a novel therapeutic approach to sensitize EBV+ lymphomas to immunotherapy.}}, added-at = {2020-04-24T04:17:52.000+0200}, author = {Dalton, Tanner and Doubrovina, Ekaterina and Pankov, Dmitry and {Reynolds, Raymond Cullen}, III and Scholze, Hanna and Selvakumar, Annamalai and Vizconde, Teresa and Savalia, Bhumesh and Dyomin, Vadim and Weigel, Christoph and Oakes, Christopher C. and Alonso, Alicia and Elemento, Olivier and Pan, Heng and Phillip, Jude M and O'Reilly, Richard J and Gewurz, Benjamin E and Cesarman, Ethel and Giulino-Roth, Lisa}, biburl = {https://www.bibsonomy.org/bibtex/22a95aebd0fe65b14e254a39acb30b3ce/bgewurz}, doi = {10.1182/blood.2019004126}, eprint = {https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2019004126/1718730/blood.2019004126.pdf}, interhash = {7e9cdba89c635edbc808df538ab387d8}, intrahash = {2a95aebd0fe65b14e254a39acb30b3ce}, issn = {0006-4971}, journal = {Blood}, keywords = {b-cell epstein-barr lmp1 myown virus}, month = {03}, note = {blood.2019004126}, timestamp = {2020-04-28T23:55:04.000+0200}, title = {{Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to viral directed immunotherapy}}, url = {https://doi.org/10.1182/blood.2019004126}, year = 2020 }