Fig. 2

Potential mechanism of combinatory synergism between three methods of immune checkpoint blockade. PD-1 or CTLA4 signaling inhibits proliferation of effector T cells. In addition, some studies have suggested that Tregs are also partly activated by PD-1 or CTLA4 signaling [100]. IDO signaling induces tumor immune tolerance by both suppressing effector T cells and activating Tregs. Therefore, if PD-1 or CTLA-4 signaling blockade is combined with an IDO inhibitor, effector T cells may be further activated and Tregs may be further suppressed. The result could be more effective reversal of immune tolerance and enhanced anti-tumor immune response. APC, antigen-presenting cell; PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1; CTLA4, cytotoxic T-lymphocyte-associated protein 4; B7-1/2, peripheral membrane proteins found on activated APCs