Unleashing antitumor T-cell activation without ensuing autoimmunity: the case for A20-deletion in adoptive CD8(+) T-cell therapy

摘要

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-kappa B activation, possessed heightened antitumor activity in vivo. The boosted immunity of A20-deleted CD8(+) T cells correlated with a heightened capacity to produce IFN gamma and TNF alpha while expressing reduced levels of the immune checkpoint molecule PD-1.