In contrast to CD28, CTLA-4 negatively regulates the activation of T cells.56 In preclinical cancer models, CTLA-4 blocking antibody treatment in mice was found to successfully prevent tumor establishment and also promote tumor rejection.57,58 However, in human clinical studies, fully humanized anti-CTLA-4 treatment, such as ipilimumab, was shown to increase the risk of autoimmune diseases such as colitis in certain treated cancer patients.59,60. Here, CD28 is linked to neoplasm.