CD4 and cancer: It has been shown that the intracytoplasmic tail of PD-L1 can trigger a signal cascade that make cancer cells resistant to interferon-mediated cytotoxicity through a STAT3/caspase-7-dependent pathway [48] and that in CD4+ T-cells binding to PD-L1 induced STAT3-dependent “back signaling” that prevented T-cell activation and polarization [49].