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  • GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism.

GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism.

Cancer cell (2019-08-27)
Laura Mondragón, Rana Mhaidly, Gian Marco De Donatis, Marie Tosolini, Pascal Dao, Anthony R Martin, Caroline Pons, Johanna Chiche, Marie Jacquin, Véronique Imbert, Emma Proïcs, Laurent Boyer, Anne Doye, Frédéric Luciano, Jaap G Neels, Frédéric Coutant, Nicole Fabien, Laura Sormani, Camila Rubio-Patiño, Jozef P Bossowski, Florian Muller, Sandrine Marchetti, Elodie Villa, Jean-François Peyron, Philippe Gaulard, François Lemonnier, Vahid Asnafi, Laurent Genestier, Rachid Benhida, Jean-Jacques Fournié, Thierry Passeron, Jean-Ehrland Ricci, Els Verhoeyen
RESUMO

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.

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