GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism
Mondragón L, Mhaidly R, De Donatis GM, Tosolini M, Dao P, Martin AR, Pons C, Chiche J, Jacquin M, Imbert V, Proïcs E, Boyer L, Doye A, Luciano F, Neels JG, Coutant F, Fabien N, Sormani L, Rubio-Patiño C, Bossowski JP, Muller F, Marchetti S, Villa E, Peyron JF, Gaulard P, Lemonnier F, Asnafi V, Genestier L, Benhida R, Fournié JJ, Passeron T, Ricci JE, Verhoeyen E.
CANCER CELL
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-kappa B pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-kappa B pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-kappa B signaling in AITL and provide a model for future AITL therapeutic investigations.
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