Imperial College London
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ProfessorHectorKeun

Faculty of Medicine, Department of Surgery & Cancer

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hilmenyuk:2017:10.1080/2162402X.2017.1365997,
author = {Hilmenyuk, T and Ruckstuhl, CA and Hayoz, M and Berchtold, C and Nuoffer, J-M and Solanki, S and Keun, HC and Beavis, PA and Riether, C and Ochsenbein, AF},
doi = {10.1080/2162402X.2017.1365997},
journal = {OncoImmunology},
title = {T cell inhibitory mechanisms in a model of aggressive Non-Hodgkin's Lymphoma},
url = {http://dx.doi.org/10.1080/2162402X.2017.1365997},
volume = {7},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A reduced immune surveillance due to immune deficiency or treatment with immunosuppressive drugs is associated with a higher risk to develop aggressive Non-Hodgkin's lymphoma (NHL). Nevertheless, NHL also develops in immunocompetent patients indicating an escape from the immune system. T cell function in advanced aggressive lymphoma is not well characterized and the molecular mechanisms how malignant B cells influence T cell function are ill-defined. We therefore studied T cell function in Eμ-myc transgenic mice that develop an aggressive B cell lymphoma with some similarities to human Burkitt-lymphoma (BL). In advanced lymphoma, the number of T cells was severely reduced and the remaining CD4+ and CD8+ T cells lost the capacity to produce effector cytokines and expand upon re-stimulation. T cells in lymphoma-bearing mice were characterized by the expression of the immune inhibitory molecules programmed death (PD)-1, 2B4 and lymphocyte activation protein (LAG)-3. The proto-oncogene c-Myc not only drives cell proliferation and disease progression but also induces apoptosis of the malignant cells. We found that apoptotic lymphoma cells release purine metabolites that inhibit T cell function. Taken together, our data document that the characteristic high cell turnover and apoptotic rate in aggressive NHL induce a severe T cell dysfunction mediated by several immune-inhibitory mechanisms including ligation of inhibitory ligands and purine metabolites. Blocking a single mechanism only partially restored T cell function and did not increase survival of lymphoma mice.
AU  - Hilmenyuk,T
AU  - Ruckstuhl,CA
AU  - Hayoz,M
AU  - Berchtold,C
AU  - Nuoffer,J-M
AU  - Solanki,S
AU  - Keun,HC
AU  - Beavis,PA
AU  - Riether,C
AU  - Ochsenbein,AF
DO  - 10.1080/2162402X.2017.1365997
PY  - 2017///
SN  - 2162-4011
TI  - T cell inhibitory mechanisms in a model of aggressive Non-Hodgkin's Lymphoma
T2  - OncoImmunology
UR  - http://dx.doi.org/10.1080/2162402X.2017.1365997
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000424080200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/57309
VL  - 7
ER  -
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