| Literature DB >> 31447347 |
Laura Mondragón1, Rana Mhaidly1, Gian Marco De Donatis1, Marie Tosolini2, Pascal Dao3, Anthony R Martin3, Caroline Pons1, Johanna Chiche1, Marie Jacquin1, Véronique Imbert1, Emma Proïcs1, Laurent Boyer1, Anne Doye1, Frédéric Luciano1, Jaap G Neels1, Frédéric Coutant4, Nicole Fabien5, Laura Sormani1, Camila Rubio-Patiño1, Jozef P Bossowski1, Florian Muller1, Sandrine Marchetti1, Elodie Villa1, Jean-François Peyron1, Philippe Gaulard6, François Lemonnier7, Vahid Asnafi8, Laurent Genestier9, Rachid Benhida3, Jean-Jacques Fournié10, Thierry Passeron11, Jean-Ehrland Ricci12, Els Verhoeyen13.
Abstract
GAPDH is emerging as a key player in T cell development and function. To investigate the role of GAPDH in T cells, we generated a transgenic mouse model overexpressing GAPDH in the T cell lineage. Aged mice developed a peripheral Tfh-like lymphoma that recapitulated key molecular, pathological, and immunophenotypic features of human angioimmunoblastic T cell lymphoma (AITL). GAPDH induced non-canonical NF-κB pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-κB pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-κB signaling in AITL and provide a model for future AITL therapeutic investigations.Entities:
Keywords: NF-κB pathway; NF-κB-inducing kinase; PD1; T follicular helper cells; angioimmunoblastic T cell lymphoma; anti-PD1 immunotherapy; germinal center B cells; glyceraldehyde-3-phosphate-dehydrogenase; glycolytic enzyme; preclinical mouse model for AITL
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Year: 2019 PMID： 31447347 DOI： 10.1016/j.ccell.2019.07.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743