The goal of this U01 and the future collaborations with the PDAC Consortium is to provide novel mechanistic insights into reprogramming the immunosuppressive tumor microenvironment of PDAC into an immunostimulatory one. Our approach to achieve this will be to use widely prescribed and inexpensive inhibitors of the angiotensin II signaling. Our preliminary data show that angiotensin II signaling mediates not only the desmoplastic reaction characteristic of PDACs, but also immunosuppression via effects on innate and adaptive immunity. The resulting data will directly inform the design of a clinical trial to test the efficacy of combining losartan—an angiotensin II signaling inhibitor—and cytotoxic agents with immune checkpoint blockers in a multi-institutional trial led by our clinical collaborators at the MGH Cancer Center. By altering the tumor microenvironment in this manner, we aim to overcome resistance to standard and emerging systemic therapies for this intractable disease. For more information click here