Purinergic signaling is a spatially organized checkpoint: co-localization of CD73+ tumor cells with CD39+ microglia amplifies extracellular adenosine that suppresses T cells via high-affinity A2A receptors and conditions myeloid cells via lower-affinity A2B; hypoxia/HIF-1α upregulates CD73, strengthening this axis—rationalizing anti-CD73 or adenosine-receptor antagonists with spatial biomarkers as inclusion/response criteria. The gene discussed is ENTPD1; the disease is neoplasm.