CHAI and LATAIE: New genetic diseases of CTLA-4 checkpoint insufficiency

Abstract

CTLA-4 is a critical inhibitory 'checkpoint' molecule of immune activation. Several recent reports have described patients with immune dysregulation and lymphoproliferative disease resulting from 2 different genetic diseases that directly or indirectly cause CTLA-4 deficiency. Numerous articles have also been published describing CTLA-4 blockade in cancer immunotherapy and its side effects, which are ultimately the consequence of treatmentinduced CTLA-4 deficiency. Here, we review these 2 diseases and CTLA-4 blockade therapy, emphasizing the crucial role of CTLA-4 in immune checkpoint regulation.