CD28 and cancer: In this context, the use of blocking antibodies, drug antagonists, dominant-negative receptors (DNR), and knocking out mechanisms such as CRISPR/Cas9 and shRNA to suppress the inhibitory checkpoints like PD-1/PDL-1 as well as administrating the costimulatory molecules like CD28 and 4-1BB, in combination with CAR-T cell would be promised in cancer treatment.