The C-terminus of c-Cbl interacts with the cytoplasmic tail of PD-1, leading to PD-1 ubiquitination and proteolysis.42 Moreover, both c-Cbl and Cbl-b downregulate PD-L1 expression after the inhibition of PI3K/Akt, Jak/Stat, and MAPK-Erk signaling.43 These findings suggest that c-Cbl/Cbl-b is negatively associated with PD-1/PD-L1 expression and that targeting c-Cbl/Cbl-b may sensitize cancer patients to ICB treatments. This evidence concerns the gene CD274 and cancer.