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We found that homozygous\n            <jats:italic toggle=\"yes\">MTAP<\/jats:italic>\n            deletion in human tumors creates a tumor microenvironment that obstructs cytosolic nucleic acid\u2013sensing pathways by down-regulating interferon regulatory factor 3 (IRF3), leading to resistance to STING agonists. Targeting polyamine biosynthesis reverses IRF3 down-regulation, restoring sensitivity to STING agonists in MTAP-deficient tumors. Our findings suggest that MTAP genetic status may inform patient responses to STING agonist therapy and offer an alternative strategy for boosting antitumor immune responses using STING agonists in\n            <jats:italic toggle=\"yes\">MTAP<\/jats:italic>\n            -deleted tumors.\n          <\/jats:p>","DOI":"10.1126\/science.adl4089","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:03:28Z","timestamp":1760033008000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists"],"prefix":"10.1126","volume":"390","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-3945","authenticated-orcid":true,"given":"Jung-Mao","family":"Hsu","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan."},{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-1943","authenticated-orcid":true,"given":"Chunxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiya","family":"Xia","sequence":"additional","affiliation":[{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan."},{"name":"Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA."},{"name":"Center for Molecular Medicine, China Medical University, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-0079","authenticated-orcid":true,"given":"Chung-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan."},{"name":"Center for Molecular Medicine, China Medical University, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-4857","authenticated-orcid":true,"given":"Wei-Chung","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan."},{"name":"Ph.D. Program for Cancer Molecular Biology and Drug Discovery, China Medical University, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6588-9785","authenticated-orcid":true,"given":"Junwei","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University; 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