Expression of CD39 and CD73 as a means of evading anti-tumor immune reponses in lung cancer (100.7)

Abstract

Abstract A major hurdle for cancer immunotherapy is the ability of tumors to inhibit anti-tumor immune responses. CD39 and CD73 are ectonucleotidases that promote the generation of extracellular adenosine from ATP. In light of the ability of adenosine to inhibit T cell responses by activating the adenosine A2a receptor (A2aR) we wanted to explore the expression of these two molecules on the surface of cancer cells. We investigated CD39 and CD73 expression and function utilizing murine and human tissues. In vitro studies revealed that Murine Lewis Lung Carcinoma cells did not express ectonucleotidases. However, upregulation of CD39 was found in vivo at multiple time points after injection into C57BL/6 mice. This expression was not T or B cell mediated as injection into RAG knockout mice produced the same expression patterns. Interestingly, characterization of multiple human lung cancer cells lines in vitro revealed near universal expression of CD73 and no CD39 expression. To determine if the upregulation of adenosine could have consequences in vivo, we injected Lewis lung carcinoma cells into A2aR knock out mice or wild-type mice treated with an adenosine receptor antagonist. In both cases improvements in tumor free and overall survival were observed. Overall our data suggests that CD39 and CD73 expression on the surface of lung cancer cells may contribute to their resistance to immunotherapy and that successful immunotherapy in lung cancer might include A2aR antagonists.