Researchers at Stanford University and the Arc Institute developed STF-1623, an ENPP1 inhibitor with ultralong tumor residence time aimed at blocking cancer cells' evasion of innate immune detection. By preventing ENPP1-mediated degradation of cGAMP, STF-1623 reactivates the STING pathway to turn immunologically 'cold' tumors 'hot,' enhancing the recruitment of tumor-infiltrating lymphocytes. This represents a novel approach to innate immune checkpoint blockade with potential to overcome resistance to current immunotherapies.