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Ionizing radiation (IR) promotes PD\u2010L1 expression in tumour cells. However, the effect of IR on macrophage PD\u2010L1 expression and the underlying mechanisms remain unclear. ATM kinase, as the key kinase for initiating DNA damage repair (DDR) process, is associated with innate immune STING axis activation. Here, we explored the molecular mechanism implicated in macrophage PD\u2010L1 expression regulated by IR as well as the role of ATM kinase in this process. IR\u2010regulated PD\u2010L1 expression in macrophages and associated signalling pathways were explored by in vitro studies using murine and human macrophage cell lines. A colorectal xenograft murine model was employed to demonstrate the impact of targeting ATM and PD\u2010L1 expression in TAMs following IR on growth of tumour in vivo<jats:italic>.<\/jats:italic> IR up\u2010regulated PD\u2010L1 expression in macrophages, which was further augmented by ATM kinase inhibition. ATM inhibition increased IR\u2010induced DNA damage, which activated STING\/interferon regulatory factor 3 (IRF3) signalling pathway and up\u2010regulated type I interferon (IFN\u2010I) expression in macrophages. IFN\u2010I bound to the IFN \u03b1 receptor 1 on macrophages, activated the downstream JAK1 and STAT1\/3 signalling and eventually led to PD\u2010L1 up\u2010expression. ATM inhibition augmented IR\u2010induced PD\u2010L1 expression in macrophages and CD8<jats:sup>+<\/jats:sup> T cell infiltration, and promoted anti\u2010tumour efficacy in vivo. These results suggested that ATM inhibition promoted IR\u2010induced PD\u2010L1 expression through the activation of innate immunity in TAMs, which provided a novel approach to enhance the anti\u2010tumour efficacy of RT.<\/jats:p>","DOI":"10.1111\/imm.13602","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T13:49:14Z","timestamp":1667483354000},"page":"346-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Ataxia telangiectasia mutated kinase\u00a0inhibition promotes <scp>irradiation\u2010induced PD\u2010L1<\/scp> expression in <scp>tumour\u2010associated<\/scp> macrophages through <scp>IFN\u2010I<\/scp>\/<scp>JAK<\/scp> signalling pathway"],"prefix":"10.1111","volume":"168","author":[{"given":"Yuke","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaihuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastric and Colorectal Surgical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengrong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Department of Biological Repositories Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Biological Repositories Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuji","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6623-9864","authenticated-orcid":false,"given":"Conghua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.211"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12658"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00156"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1405-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14292"},{"key":"e_1_2_11_7_1","first-page":"1064","article-title":"Synergizing radiation therapy and immunotherapy for curing incurable cancers. 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