Abstract B3: CD39+ cancer cells mediate immunosuppression reverted by CD39-blocking antibodies.

The CD39 and CD73 ectonucleotidases hydrolyze extracellular ATP and ADP into immunosuppressive adenosine that binds adenosine receptor and inhibits T cell and NK cell responses. It has been demonstrated that CD39+ Tregs are increased in some human cancers and participate to immunosuppression. The importance of CD39+ Tregs in promoting tumor growth and metastasis has been evidenced in several models in vivo (for a review, see Bastid J et al., Oncogene, 2012). Here, we addressed whether CD39 is expressed by tumor cells and whether CD39+ tumor cells mediate suppression through the CD39-adenosine pathway. Immunohistochemical staining of normal and tumor tissues revealed that CD39 is upregulated in several types of human cancer. In cancer specimens, CD39 is expressed by infiltrating lymphocytes, tumor stroma and tumor cells, whereas its expression in normal samples is absent or weak and mostly limited to vascular endothelia. The expression of CD39 at the cell surface of tumor cells was further directly demonstrated by flow cytometry in human cancer cell lines. We evidenced that CD39+ tumor cells express functional CD39 and inhibit CD4 and CD8 T cell function in a CD39-dependant manner. Treatment with CD39-blocking antibodies was able to alleviate CD39+ tumor cell-mediated inhibition of CD4 and CD8 T cells in co-culture experiments. In conclusion, interfering with the CD39-adenosine pathway could represent a novel immunotherapy strategy for inhibiting Treg and tumor cell-mediated immunosuppression. Furthermore, these results support the ongoing development of CD39-blocking monoclonal antibodies as potential anticancer drugs. Citation Format: Anne Regairaz, Caroline Laheurte, Nathalie Bonnefoy, Jean-Francois Eliaou, Gilles Alberici, Armand Bensussan, Jeremy Bastid. CD39+ cancer cells mediate immunosuppression reverted by CD39-blocking antibodies. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B3.