Inhibition of specific immune checkpoint proteins of the B7/CD28 family like programmed cell death protein-1 (PD-1) and its ligand PD-L1, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and more recently LAG-3 using monoclonal antibodies has revolutionized treatment for cancer patients with advanced or metastatic tumors. Here, CD28 is linked to metastatic neoplasm.