CD80 and cancer: Therefore, by disrupting PD-L1:CD80 heterodimers, anti-PD-L1 mAbs licenses high-avidity CD80:CTLA-4 interactions which triggers Treg-mediated depletion of CD80 from APCs and inhibits CD28 co-stimulation.458 Since this CD80 depletion by anti-PD-L1 is CTLA-4 dependent and can be reversed by CTLA-4 blockade,341,463 it provides a rationale for co-blocking PD-L1 and CTLA-4 in cancer immunotherapy.