The Effects of CD73 on Gastrointestinal Cancer Progression and Treatment

Figure 1

CD73 influencing immune cell expression in the tumor microenvironment. Hypoxic TME upregulates the expression of HIF-1α and CD73 and causes more ATP release from dead tumor cells. Through the CD39 and CD73 on immune cells, ATP is hydrolyzed to adenosine. On NK cells, adenosine activates A3R and causes the upregulation of IL-12 which enhances the cytotoxicity of NK cells. On Foxp3+Treg cells, adenosine activates A2AR and increases the expression of immunosuppression checkpoints such as PD-1 and CTLA-4. Adenosine can also activate A2AR on T effector cells and downregulate the expression of NF-κB in T effector cells, and then decrease the production of cytokines such as TNF-α and IFN-γ. On MDS cells, adenosine can activate A2BR and increase the production of cytokines such as TNF-α, HIF-α, and TGF-β while some of these cytokines in turn can regulate the expression of CD39 and CD73 on MDS cells and Th17 cells. On Th17 cells, adenosine can activate A2AR and decrease the production of cytokines such as IL-6 which also in turn can regulate the expression of CD39 and CD73 on Th17 cells.