Fig. 2
From: Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future
Hypoxia. Hypoxia driven upregulation of CD73 leads to increased adenosine binding at the A2A receptor (A2AR). The A2AR inhibits NK cell function through the SOCS pathway via downregulation of activating receptors. Increased expression of the hypoxia inducible factor 1-alpha (HIF1α) in leukemic blasts results in upregulation of ADAM10 and subsequent cleavage of MIC-A—the canonical ligand for the NK cell activating receptor NKG2D