Drug targets for Cancer: adenosine A2a receptor

Drug Targets for Cancer: adenosine A2a receptor and Cancer

The A2A adenosine receptor plays a critical and non-redundant role in suppressing inflammation at sites of hypoxia and tissue damage. The cancer microenvironment has high levels of adenosine as a result of hypoxia and ectopic expression of enzymes responsible for the generation of extracellular adenosine. It is observed that mice lacking the A2A adenosine receptor showed significantly delayed growth of lymphoma cells when compared to WT mice. Furthermore, when immunized with a low dose of tumor or with an irradiated GM-CSF–secreting cancer vaccine, A2A receptor null mice showed significantly enhanced protection from a subsequent high-dose challenge from both immunogenic and poorly immunogenic cancer lines. This increase in protection was accompanied by an increase in the number of tumor-antigen-specific CD8 T cells at the vaccine-site draining lymph node. Finally, It was found that A2A receptor null mice displayed more robust anti-cancer responses than WT mice when they were treated with a soluble B7-DC/Fc fusion protein designed to antagonize B7-H1-mediated co-inhibition. This combinatorial immunotherapy strategy could also be recapitulated with pharmacological A2A receptor blockade paired with B7-DC/Fc administration. In light of these data, we believe that blockade of the A2A adenosine receptor is an attractive target for tumor immunotherapy that synergizes with other immunomodulatory approaches currently in clinical trials.

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Drug targets for cancer: adenosine A2a receptor research reagents

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Drug Targets for Cancer: adenosine A2a receptor Related Reference

Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD. Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer immunology, immunotherapy?: CII. 2012;61(6):917-926.

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Drug Targets for Cancer