{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:11:48Z","timestamp":1792145508391,"version":"4.4.0"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA240515,U01CA216449,R21CA252010,R50CA251960,P30CA046592"],"award-info":[{"award-number":["R01CA240515,U01CA216449,R21CA252010,R50CA251960,P30CA046592"]}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"crossref","award":["I01 BX005267"],"award-info":[{"award-number":["I01 BX005267"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["R01CA240515,U01CA216449,R21CA252010,R50CA251960,P30CA046592"],"award-info":[{"award-number":["R01CA240515,U01CA216449,R21CA252010,R50CA251960,P30CA046592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    Radiotherapy induces a type I interferon\u2013mediated (T1IFN-mediated) antitumoral immune response that we hypothesized could be potentiated by a first-in-class ataxia telangiectasia mutated (ATM) inhibitor, leading to enhanced innate immune signaling, T1IFN expression, and sensitization to immunotherapy in pancreatic cancer. We evaluated the effects of AZD1390 or a structurally related compound, AZD0156, on innate immune signaling and found that both inhibitors enhanced radiation-induced T1IFN expression via the POLIII\/RIG-I\/MAVS pathway. In immunocompetent syngeneic mouse models of pancreatic cancer, ATM inhibitor enhanced radiation-induced antitumoral immune responses and sensitized tumors to anti\u2013PD-L1, producing immunogenic memory and durable tumor control. Therapeutic responses were associated with increased intratumoral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell frequency and effector function. Tumor control was dependent on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, as therapeutic efficacy was blunted in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013depleted mice. Adaptive immune responses to combination therapy provided systemic control of contralateral tumors outside of the radiation field. Taken together, we show that a clinical candidate ATM inhibitor enhances radiation-induced T1IFN, leading to both innate and subsequent adaptive antitumoral immune responses and sensitization of otherwise resistant pancreatic cancer to immunotherapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168824","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T12:00:23Z","timestamp":1708430423000},"source":"Crossref","is-referenced-by-count":17,"title":["Potentiating the radiation-induced type I interferon antitumoral immune response by ATM inhibition in pancreatic cancer"],"prefix":"10.1172","volume":"9","author":[{"given":"Qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology and"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, 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