Herein, we provide evidence demonstrating that INDO-mediated COX2 inhibition augments MUS81-mediated cytoplasmic tumor DNA accumulation and cGAS/STING/type I IFN, which restored tumor immune surveillance via potent antitumor innate and adaptive immune responses in irradiated 4T1 TNBC tumors. The gene discussed is PTGS2; the disease is neoplasm.