Epigenetic reprogramming sensitizes immunologically silent EBV(+) lymphomas to virus-directed immunotherapy Journal Article

   


Authors: Dalton, T.; Doubrovina, E.; Pankov, D.; Reynolds, R.; Scholze, H.; Selvakumar, A.; Vizconde, T.; Savalia, B.; Dyomin, V.; Weigel, C.; Oakes, C. C.; Alonso, A.; Elemento, O.; Pan, H.; Phillip, J. M.; O'Reilly, R. J.; Gewurz, B. E.; Cesarman, E.; Giulino-Roth, L.
Article Title: Epigenetic reprogramming sensitizes immunologically silent EBV(+) lymphomas to virus-directed immunotherapy
Abstract: Despite advances in T-cell immunotherapy against Epstein-Barr virus (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 (BL) sensitized cells to lysis by EBV-specific cytotoxic T cells (EBV-CTLs). In latency I BL 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. © 2020 by The American Society of Hematology.
Journal Title: Blood
Volume: 135
Issue: 21
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2020-05-21
Start Page: 1870
End Page: 1881
Language: English
DOI: 10.1182/blood.2019004126
PUBMED: 32157281
PROVIDER: scopus
PMCID: PMC7243148
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085264822&doi=10.1182%2fblood.2019004126&partnerID=40&md5=6467ba591d7432ee1ed171d3f56b550e
Notes: Article -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Vadim G Dyomin
    16 Dyomin
  2. Ekaterina Doubrovina
    101 Doubrovina
  3. Annamalai Selvakumar
    68 Selvakumar
  4. Dmitry D. Pankov
    22 Pankov
  5. Richard O'Reilly
    748 O'Reilly
  6. Teresa Vizconde
    2 Vizconde
  7. Bhumesh Mansukhbhai Savalia
    1 Savalia
Related MSK Work