{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:25:10Z","timestamp":1785428710878,"version":"3.56.0"},"reference-count":56,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["DP5 DO024576"],"award-info":[{"award-number":["DP5 DO024576"]}]},{"name":"NIH","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]},{"name":"NIH","award":["P50 DE026787"],"award-info":[{"award-number":["P50 DE026787"]}]},{"name":"NIH","award":["U01 CA233102"],"award-info":[{"award-number":["U01 CA233102"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,8,25]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of interferon genes (STING) activation. We investigated whether combining RT with an ataxia-telangiectasia mutated inhibitor promoted these effects and amplified tumor immunity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mice-bearing syngeneic flank tumors (MOC2 head and neck squamous cell carcinoma or B78 melanoma) were treated with tumor-directed RT and oral administration of AZD0156. Specific immune cell depletion, type 1 interferon receptor 1 knock-out mice (IFNAR1-KO), and STING-deficient tumor cells were used to investigate tumor-immune crosstalk following RT and AZD0156 treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Combining RT and AZD0156 reduced tumor growth compared with RT or AZD0156 alone in mice bearing MOC2 or B78 tumors. Low-dose AZD0156 (1\u2013100\u2009nM) alone did not affect tumor cell proliferation but suppressed tumor cell clonogenicity in combination with RT. Low-dose AZD0156 with RT synergistically increased IFN-\u03b2, major histocompatibility complex (MHC)-I, and programmed death-ligand 1 (PD-L1) expression in tumor cells. In contrast to wild-type mice, IFNAR1-KO mice showed reduced CD8+T\u2009cell tumor infiltration and poor survival following RT+AZD0156 treatment. CD8+T\u2009cell depletion reduced antitumor response during RT+AZD0156 treatment. STING-deficient MOC2 (MOC2-STING+\/\u2013) or B78 (B78-STING\u2013\/\u2013) tumors eliminated the effects of RT+AZD0156 on the expression of IFN-\u03b2, MHC-I, and PD-L1, and reduced CD8+T\u2009cell infiltration and migration. Additional anti-PD-L1 therapy promoted antitumor response by elevation of tumor-MHC-I and lymphocyte activation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Combined radiation and AZD0156 increase STING-dependent antitumor response. Tumor-derived cell-autonomous IFN-\u03b2 amplification drives both MHC-I and PD-L1 induction at the tumor cell surface, which is required by anti-PD-L1 therapy to promote antitumor immune response following RT and AZD0156 combination therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-007474","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T01:45:52Z","timestamp":1695174352000},"page":"e007474","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["ATM inhibition augments type I interferon response and antitumor T-cell immunity when combined with radiation therapy in murine tumor models"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02588105","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4147-9735","authenticated-orcid":false,"given":"Won 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