The invention comprises describes the utility of adenosine deaminase enzyme to deplete Ado within the tumor microenvironment. This therapeutic mechanism represents a fundamentally new form of immunotherapy that acts by destroying a pro-tumor (and pro-metastatic) and anti-inflammatory small molecule. We believe that this mechanism if successful has the potential to fundamentally alter cancer therapy and is easily combined with other forms of treatment (both conventional chemotherapy and antibody immunotherapy) to tackle aggressive solid tumors to reduce patient mortality.