A major finding in the current report reflects the regulatory action of several ISGs (ARG2, ISG15, NOS2, PD-L1, PTGS2/COX2) that serve to limit the anti-tumor activity of STING agonists in vivo, with targeted ISG antagonists improving treatment outcomes when applied in combination with STING agonist ADU-S100. Here, NOS2 is linked to neoplasm.