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 activity in 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.