{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:42:37Z","timestamp":1787928157655,"version":"build-2784847793"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan","award":["110-2320-B-037-023"],"award-info":[{"award-number":["110-2320-B-037-023"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["KMU-M112029"],"award-info":[{"award-number":["KMU-M112029"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["110-2320-B-037-023"],"award-info":[{"award-number":["110-2320-B-037-023"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["KMU-M112029"],"award-info":[{"award-number":["KMU-M112029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Immune checkpoint blockade (ICB) therapy can improve the survival of cancer patients with a high tumor mutation burden (TMB-H) or deficiency in DNA mismatch repair (dMMR) in their tumors. However, most cancer patients without TMB-H and dMMR do not benefit from ICB therapy. The inhibition of ATM can increase DNA damage and activate the interferon response, thus modulating the tumor immune microenvironment (TIME) and the efficacy of ICB therapy. In this study, we showed that ATM inhibition activated interferon signaling and induced interferon-stimulated genes (ISGs) in cisplatin-resistant and parent cancer cells. The ISGs induced by ATM inhibition were correlated with survival in cancer patients who received ICB therapy. In oral cancer, high expressions of ISG15, IFI27, and OASL were associated with low expressions of ATM, the activation of inflamed immune pathways, and increased tumor-infiltrating scores of CD8+ T, natural killer, and dendritic cells. The high expressions of ISG15, IFI27, and OASL were also correlated with complete remission in patients with cervical cancer treated with cisplatin. These results suggest that ATM inhibition can induce the interferon response and inflamed TIME, which may benefit ICB therapy.<\/jats:p>","DOI":"10.3390\/cells12091288","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:02:31Z","timestamp":1682942551000},"page":"1288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["ATM Inhibition-Induced ISG15\/IFI27\/OASL Is Correlated with Immunotherapy Response and Inflamed Immunophenotype"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-1587","authenticated-orcid":false,"given":"Chi-Han","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Cian","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4028-8143","authenticated-orcid":false,"given":"Jun-Kai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Chia","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau-Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-2187","authenticated-orcid":false,"given":"Chang-Shen","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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