Figure 1.

Mechanisms of AML-induced immunosuppression. There are several immunosuppressive pathways that have been described for AML. Both direct and indirect mechanisms can ultimately lead to AML immune escape. (A) Enzymes such as arginase II and IDO can be expressed by AML blasts, leading to production of metabolites that hinder effector cell function and proliferation, while polarizing the tumor microenvironment to become more immunosuppressive by favoring Treg and MDSC expansion. (B) AML blasts can express ectonucleotideases such as CD38, CD39, and CD73 that are involved in the breakdown of ATP and NAD+ to adenosine, which subsequently dampens effector cell function and enhances the activity of immunosuppressive cells. (C) Inhibitory ligands such as PD-L1 and PD-L2 can be expressed by AML blasts, and upon binding with their cognate PD-1 receptor may lead to effector cell suppression. Expression of other inhibitory receptors such as GITR, TIGIT, TIM-3, and CTLA-4 have also been shown in AML. (D) AML blasts are able to produce large amounts of ROS that subsequently trigger apoptosis of effector cells. (E) AML blasts can also downregulate their MHCI and/or MHCII expression, thus impairing their antigen presentation resulting in immune evasion.