The Role of Adenosine A2BR in Metastatic Melanoma

Adenosine signaling has been shown in many cancers including melanoma and has been associated with poor prognosis and increased risk of metastasis. Evidence indicates that adenosine receptor A2AR plays a role in inhibiting immune cells whereas A2BR is likely most critical on tumor cells and tumor endothelium. We propose that elimination of adenosine A2B receptor signaling in endothelial cells and tumor cells will result in a decrease of primary melanoma and metastasis. We were interested in the relevance of A2BR in the context of immunotherapy checkpoint inhibitors anti-PD1 or anti-CTLA4 or Braf inhibitors. We found that knocking down A2BR expression in melanoma cells SM1WT1 LWT1 did not change the growth of primary tumor nor experimental metastasis when compared to control tumor. Additionally, A2BR knocked out in the endothelium or the whole host did not affect primary tumor growth or metastasis of melanoma cell lines SM1WT1, B16F10 and HCMel12. Therefore, A2BR does not play a significant role in melanoma growth or metastasis.