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Pathogenesis of Virus-Associated Tumors

Division of Pathogenesis of Virus Associated Tumors

Prof. Dr. Dr. Henri-Jacques Delecluse

Primary squamous epithelial cells infected with a recombinant Epstein-Barr virus tagged with a GFP gene.
© dkfz.de

The Epstein-Barr virus (EBV) infects the large majority of the population and is responsible for 1 to 2% of all cancers. Our projects aim at understanding how the virus induces these tumors and how they can be prevented. We previously found that the multiple microRNAs encoded by the virus modulate its oncogenic properties. More recently, we moved our attention to the contribution of lytic replication, the process that leads to the production of viruses, to cancer development. We showed that the EBV infectious particles can deregulate the centrosome machinery and induce genetic instability. This newly identified cancer risk is independent of the viral genome and could significantly expand the range of diseases caused by the virus. EBV is known to induce Hodgkin’s lymphomas and large cell lymphomas, particularly in immunocompromised patients and a particular type of gastric carcinoma all over the world. However, some EBV-associated tumors such as nasopharyngeal carcinoma and Burkitt’s lymphomas have a strikingly heterogeneous geographic distribution. We have shown that some of these differences can be explained by the infection with particular types of Epstein-Barr viruses. This led to the development of Epstein-Barr virus-like particles (VLPs) from these highly pathogenic strains that can be used as preventative vaccines. We have also designed a new immunotherapeutic approach that uses EBV antigens to induce an immune response against B cell lymphomas.

FUTURE OUTLOOK
While we will continue our projects on the molecular mechanisms of EBV-induced cancer, we will focus on the development of clinically relevant projects including the study of EBV strains found in diseased patients, the development of an EBV-specific vaccine and of immunotherapeutic strategies based on antigen-loaded antibodies.

Contact

Prof. Dr. Dr. Henri-Jacques Delecluse
Pathogenesis of Virus Associated Tumors (F100)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4870

Selected Publications

  • Shumilov A, Tsai MH, Schlosser YT, Kratz AS, Bernhardt K, Fink S, Mizani T, Lin X, Jauch A, Mautner J, Kopp-Schneider A, Feederle R, Hoffmann I, Delecluse HJ. Epstein-Barr virus particles induce centrosome amplification and chromosomal instability. Nat Commun. 2017 Feb 10;8:14257
  • Li Z, Tsai MH, Shumilov A, Baccianti F, Tsao SW, Poirey R, Delecluse HJ. Epstein-Barr virus ncRNA from a nasopharyngeal carcinoma induces an inflammatory response that promotes virus production. Nat Microbiol. 2019 Sep 9.
  • van Zyl DG, Tsai MH, Shumilov A, Schneidt V, Poirey R, Schlehe B, Fluhr H, Mautner J, Delecluse HJ. Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. PLoS Pathog. 2018 Dec 6;14(12)
  • Schneidt V, Ilecka M, Dreger P, van Zyl DG, Fink S, Mautner J, Delecluse HJ. Antibodies conjugated with viral antigens elicit a cytotoxic T cell response against primary CLL ex vivo.Leukemia. 2019 Jan;33(1):88-98
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