Unleashing antitumor T-cell activation without ensuing autoimmunity: the case for A20-deletion in adoptive CD8+T-cell therapy.
Mechanisms controlling immune reactivity prevent excessive inflammation and autoimmunity, but generally dampen antitumor activity. We recently showed that adoptively transferred antitumor CD8+T cells harboring a deletion of A20/Tnfaip3, a molecule controlling NF-κB activation, possessed heightened antitumor activityin vivo. The boosted immunity of A20-deleted CD8+T cells correlated with a heightened capacity to produce IFNγ and TNFα while expressing reduced levels of the immune checkpoint molecule PD-1.
Centre d'Immunologie de Marseille-Luminy (CIML); UM2 Aix-Marseille Université ; Marseille Cedex, France ; INSERM U1104 ; Marseille, France ; CNRS UMR7280 ; Marseille, France.
Grégory
G
Verdeil
Centre d'Immunologie de Marseille-Luminy (CIML); UM2 Aix-Marseille Université ; Marseille Cedex, France ; INSERM U1104 ; Marseille, France ; CNRS UMR7280 ; Marseille, France.
Anne-Marie
AM
Schmitt-Verhulst
A20/Tnfaip3; PD-1; adoptive T cell therapy; autoimmunity; melanoma