Radiation, Adenosine Signaling, and Immunosuppressive Changes to the Tumor Microenvironment

Radiation induces an immunosuppressive TME, increasing the abundance of PMN-MDSCs and M-MDSCs and activating adenosine signaling. Radiation increases the expression of adenosine receptors on CD45+ TILs at the transcriptomic level and cell surface expression of CD73 on monocytes and A2AR on granulocytes. Treatment of human PBMCs with adenosine receptor agonist resulted in loss of effector T-cell function and suppressive changes to cytokine milieu. These data suggest a mechanistic link between radiation, adenosine signaling and the myeloid compartment.