CTLA4 and cancer: The CDK4/6 inhibitor palbociclib inhibits cyclin D-CDK4-SPOP-FZR1 pathway-mediated PD-L1 ubiquitination and degradation, which increases PD-L1 level and sensitizes CT26-implanted tumor to anti-PD-1 therapy.33 Lastly, CTLA-4 blockade antibodies used for cancer immunotherapy often induce severe immunotherapy-related adverse effects (irAEs).128,129 A recent study showed irAE-prone CTLA-4 blocking antibodies induced lysosomal degradation of CTLA-4, while non-irAE-prone antibodies allowed CTLA-4 recycling in an LBRA-dependent manner.