PMC:6562565 / 73564-74675 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6562565","sourcedb":"PMC","sourceid":"6562565","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6562565","text":"Adenosine is critically involved in a range of physiologic processes including wound healing, and its levels are tightly regulated under homeostatic conditions. In solid tumors, however, adenosine concentration is significantly elevated, predominantly due to stress-induced ATP release coupled with the overexpression of nucleotidases, such as CD39 and CD73 that contribute to its catabolism. Primarily by engaging A2AR and A2BR, also overexpressed in the TME as a result of hypoxia and inflammation, adenosine diminishes the activity of protective immune infiltrates, such as T cells, NK cells and DCs, while boosting the inhibitory capacity of immunosuppressive subsets, including Tregs and MDSCs. For instance, A2AR and A2BR-induced cAMP accumulation within T cells blunts their differentiation, proliferation, cytokine production and target cell killing, predominantly through PKA activation. Along with establishing an anti-inflammatory and tolerogenic TME, adenosine also promotes blood vessel formation and assists tumors in subverting adjacent fibroblasts to further support tumor growth and metastasis.","tracks":[]}