CD28 and cancer: Both CD28 and B7 form a large family of structurally related proteins with costimulatory or coinhibitory functions.97 CTLA4 and PD1 are members of the CD28 family that serve as key coinhibitory receptors and are also known as immune checkpoints.2 Major breakthrough in cancer immunotherapy came from the successful treatment of advanced cancer patients with the ICIs anti-CTLA4 and anti-PD-1.67 Recent studies have also provided new insight into the mechanisms that regulate the fate and function of these immunosuppressive receptors.