CTLA4 and melanoma: CTLA-4 acts early duringthe priming phase of antigen presentation and following T-cellreceptor–peptide complex engagement, it is rapidly mobilized to the cellsurface, allowing feedback inhibition to occur within an hour of antigen presentation.34 Therapeutic anti-CTLA-4 monoclonal antibodies have shown clinicalactivity in advanced melanoma, most likely via disruptingthe CD28 activation on T cells as well as through depletion of regulatory Tcells (T-regs) in the tumor microenvironment.35