biostudies-literatureGirard MCanadian Institutes of Health Research CanadaCanadian Cancer SocietyCanadian Institutes of Health ResearchUniversity of TorontoCIHR3634-3646https://www.ebi.ac.uk/biostudies/studies/S-EPMC12726076biostudies-literatureUnknown214(12)The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, a sensor of cytosolic DNA, orchestrates the production of proinflammatory cytokines, chemokines, and type I interferons (IFN-Is), thereby contributing to spontaneous tumor surveillance. Intratumoral delivery of synthetic STING agonists induces IFN-I-dependent tumor regression in preclinical cancer models and is being tested clinically. In this study, we investigate the role of monocytic lineage cells (MCs) in response to STING agonist induced IFN-I signaling. We show that CCR2-deficient mice, lacking inflammatory MCs in the periphery, or Lyz2-Cre-IFNAR1fl/fl mice in which IFN-I signaling in monocytes is reduced, exhibit impaired responses to STING agonist therapy of MC38 and/or B16F10 tumors. STING agonist treJournal of immunology (Baltimore, Md. : 1950)STING agonists drive recruitment and intrinsic type I interferon responses in monocytic lineage cells for optimal anti-tumor immunity.PMC12726076FDN-143250706759PJT 190128PJ4-185649FDN-143250, PJ4-185649Yeung KKMLiu MGirard MWatts THYu TGao WBatista NVLamorte SMcGaha TLfalseSTING agonists drive recruitment and intrinsic type I interferon responses in monocytic lineage cells for optimal anti-tumor immunity.The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, a sensor of cytosolic DNA, orchestrates the production of proinflammatory cytokines, chemokines, and type I interferons (IFN-Is), thereby contributing to spontaneous tumor surveillance. Intratumoral delivery of synthetic STING agonists induces IFN-I-dependent tumor regression in preclinical cancer models and is being tested clinically. In this study, we investigate the role of monocytic lineage cells (MCs) in response to STING agonist induced IFN-I signaling. We show that CCR2-deficient mice, lacking inflammatory MCs in the periphery, or Lyz2-Cre-IFNAR1fl/fl mice in which IFN-I signaling in monocytes is reduced, exhibit impaired responses to STING agonist therapy of MC38 and/or B16F10 tumors. STING agonist tre2025-01-01T00:00:00Z2025 Dec2026-06-06T04:36:14.082Z2026-05-25T03:12:04.714ZS-EPMC127260764063309110.1093/jimmun/vkaf131