Although these findings seem to be counterintuitive as increasing concentrations of CTLA-4 should inhibit T-lymphocyte activity, some studies have suggested that, while in the resting T-lymphocytes only sCTLA-4 is expressed, inhibiting CD28-ligand interactions, in later tumor phases, mCTLA-4 is overexpressed, with sCTLA-4 interfering with mCTLA-4-ligand interactions, thus enhancing T-lymphocyte reactivity by preventing the transduction of inhibitory signals18,22,23. This evidence concerns the gene CD28 and neoplasm.