CD28 and neoplasm: Tumor localized costimulation to enhance tumor-infiltrating T cell effector function is a promising therapeutic approach and targeting of both CD28 and ICOS in this way could provide therapeutic advantages as each has been shown to serve non-overlapping functions with CD28 contributing to enhanced IL2 production, cell cycle progression and survival (32, 33), while ICOS seems to play a greater role in maintaining differentiated T cell phenotypes (33).