Blockade of A 2A receptors potently suppresses the metastasis of CD73 + tumors

• DOI: 10.1073/pnas.1308209110
• Publication Date: 2013-08-21T02:34:43Z
• Authors: Paul A. Beavis; Upulie Divisekera; Christophe Paget; Melvyn T. Chow; Liza B. John; Christel Devaud; Karen Dwyer; John Stagg; Mark J. Smyth; Phillip K. Darcy
• Keywords: Adenosine A2A receptor; Granzyme

CD73 inhibits antitumor immunity through the activation of adenosine receptors expressed on multiple immune subsets. also enhances tumor metastasis, although nature subsets and receptor subtypes involved in this process are largely unknown. In study, we revealed that A2A/A2B antagonists were effective reducing metastasis tumors expressing endogenously (4T1.2 breast tumors) when was ectopically (B16F10 melanoma). A2A(-/-) mice strongly protected against indicating host A2A enhanced metastasis. blockade natural killer (NK) cell maturation cytotoxic function vitro, reduced a perforin-dependent manner, NK expression granzyme B vivo, suggesting antimetastatic effect due to function. Interestingly, A2B had no cytotoxicity, an cell-independent mechanism contributed increased CD73(+) tumors. Our results thus promotes mechanisms, including suppression Furthermore, our data suggest or may be useful for treatment metastatic disease. Overall, study has potential therapeutic implications given have already entered clinical trials other settings.