Adenosine receptors in blood cells: Biomarkers and beyond

The identification of reliable, non-invasive biomarkers that reflect molecular alterations in deep and inaccessible tissues remains a major challenge in translational medicine. In this context, peripheral blood cells have emerged as valuable surrogates of tissue-level pathophysiology. Among molecular systems expressed in circulating cells, adenosine receptors (ARs) represent particularly attractive candidates due to their central role in regulating inflammation, immune responses, vascular function, and tissue homeostasis. This review focuses on the expression and functional modulation of AR subtypes in peripheral blood mononuclear cells and platelets, highlighting their potential as translational biomarkers across a wide spectrum of human diseases. Accumulating evidence demonstrates that disease-associated alterations of A_2A and A₃ ARs in circulating cells frequently mirror receptor remodeling occurring in the brain, cardiovascular system, inflamed tissues, and tumors. In neurodegenerative and cardiovascular disorders, peripheral A_2AAR dysregulation reflects central or myocardial changes and correlates with disease severity and progression. In contrast, the A₃AR shows a remarkable and consistent parallel overexpression in both pathological tissues and circulating immune cells in cancer and chronic inflammatory diseases, supporting its value as a circulating biomarker of systemic pathologies. Beyond their diagnostic and prognostic relevance, ARs also represent actionable pharmacological targets, bridging biomarker discovery with therapeutic intervention. Collectively, this evidence positions peripheral ARs profiling as a potential tool for non-invasive disease monitoring and for guiding personalized translational pharmacology strategies.