In most cancers, except ACC, DLBC, and THYM, robust and significant relationships existed between CD161 and recognized immune checkpoints including B- and T-lymphocyte attenuator (BTLA), CD244, inducible T cell costimulator (ICOS), CD40 ligand, CD48, CD28, CD200 receptor 1, transmembrane and immunoglobulin domain containing 2 (TMIGD2), CD27, TIGIT, and CD86. The gene discussed is CD28; the disease is cancer.