CTLA4 and autoimmune disease: Unlike most cell-surface molecules, CTLA-4 recycles between the cell surface and endosomes,35 where it is prevented from lysosomal degradation and recycles back to the cell surface by binding to the lipopolysaccharide-responsive and beige-like anchor (LRBA) protein.8,36 Since genetic mutations in either CTLA-45,8 or LRBA8,36 cause autoimmune diseases in human, we hypothesize that anti-CTLA-4-induced irAE may relate to antibody-mediated disruption of CTLA-4 recycling.