Fig. 3

CD39, CD73, and adenosine mediated immunomodulatory of mesenchymal stromal/stem cells (MSCs) on T cells, macrophages, and osteoclasts. Extracellular ATP is first converted to ADP and then to AMP through CD39. The produced AMP is used as a substrate for the function of CD73 and leads to the production of adenosine. Adenosine receptor (A2AR) can be expressed on the surface of various cells, including immune cells and tumor cells. The binding of extracellular-produced adenosine to A2AR on the surface of tumor cells can increase their survival and proliferation of tumor cells and facilitate epithelial-mesenchymal transition (EMT). Also, its binding to immune cells expressed A2AR can lead to reduced survival and production of inflammatory cytokines by inhibiting pathways related to mTORC and NF-κB. It seems that tumor cells, by expressing CD39 and CD73, help their immune escape. MSCs also express CD39 and CD73, and by producing adenosine, they affect the functions of immune cells, including T cells, macrophages, and osteoclasts. Adenosine produced by MSCs inhibits the functions of Th17 and M1 macrophages while they increase the functions of regulatory T cells and M2 macrophages. Adenosine can also reduce the function and proliferation of osteoclasts. It has also been shown that MSCs that produce adenosine can reduce the aggregation and activation of platelets