Adenosine Pathway as a prognostic biomarker and an actionable target to overcome “immune escape” of human tumors: the Mesothelioma model.

Malignant pleural mesothelioma is an aggressive cancer and, for this disease, chemotherapy, surgery and radiotherapy are not curative. During the last years, numerous of studies have focused on immune therapies exploiting the use of immune checkpoint inhibitors. So far, these treatments are based on the use of molecules that inhibit proteins and receptors such as PD-1, PD-L1 and CTLA-4 [1]. Thus, there is the urgent need to find other immune targets. The purinergic pathway is a field of great interest as in fact there is evidence that the hypoxic environment of tumors induces increased expression of CD73 and CD39 (enzymes that produce adenosine starting from ATP) which promote the increase in extracellular adenosine [2]. High levels of adenosine are characteristic of the tumor microenvironment and induce immunosuppressive signals promoting growth and progression of tumors. For this reason [3], inhibitors of the purinergic pathway drawing attention to restore immune response to cancer cells. Our study is aimed at the identification of adenosine pathway members in MPM tissue and if this same pathway is active in this tumor. We have detected high expression of the Adenosine receptors and CD73 in MPM cells. Accordingly, treatment with the A2Br antagonist (MRS1754) provided the evidence that adenosine signaling is active in MPM cells and is a potential novel druggable target against MPM.