ICOS and neoplasm: Additionally, there are agonists of costimulatory molecules to enhance the immune checkpoint signaling in the tumor microenvironment, such as 4-1BB (CD137), OX40 (a member of the tumor necrosis factor receptor superfamily 4, CD134), glucocorticoid-induced tumor necrosis factor receptor (GITR, a type I transmembrane protein), inducible T cell costimulator (ICOS), CD40 and CD28 [6].