CTLA4 and neoplasm: It is thus believed that CTLA-4 provides the regulatory braking in proportion to the acceleration received from CD28 and, in contrast to PD-1/PD-L1 axis which function at the peripheral tissues and tumor site, CTLA-4 is regarded as a negative regulator of T-cell function at the site of T-cell priming when naïve T-cells are primed when they are engaged with the peptide-MHC-APC.