{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:14:33Z","timestamp":1792793673627,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA236367"],"award-info":[{"award-number":["R01CA236367"]}]},{"name":"National Cancer Institute","award":["R01CA204173"],"award-info":[{"award-number":["R01CA204173"]}]},{"name":"National Cancer Institute","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,22]]},"abstract":"<jats:p>\n                    Inhibitors of the DNA damage signaling kinase ATR increase tumor cell killing by chemotherapies that target DNA replication forks but also kill rapidly proliferating immune cells including activated T cells. Nevertheless, ATR inhibitor (ATRi) and radiotherapy (RT) can be combined to generate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013dependent antitumor responses in mouse models. To determine the optimal schedule of ATRi and RT, we determined the impact of short-course versus prolonged daily treatment with AZD6738 (ATRi) on responses to RT (days 1\u20132). Short-course ATRi (days 1\u20133) plus RT caused expansion of tumor antigen\u2013specific, effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the tumor-draining lymph node (DLN) at 1 week after RT. This was preceded by acute decreases in proliferating tumor-infiltrating and peripheral T cells and a rapid proliferative rebound after ATRi cessation, increased inflammatory signaling (IFN-\u03b2, chemokines, particularly CXCL10) in tumors, and an accumulation of inflammatory cells in the DLN. In contrast, prolonged ATRi (days 1\u20139) prevented the expansion of tumor antigen\u2013specific, effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the DLN, and entirely abolished the therapeutic benefit of short-course ATRi with RT and anti\u2013PD-L1. Our data argue that ATRi cessation is essential to allow CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses to both RT and immune checkpoint inhibitors.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165615","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T14:01:08Z","timestamp":1676988068000},"source":"Crossref","is-referenced-by-count":42,"title":["The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy"],"prefix":"10.1172","volume":"8","author":[{"given":"Frank P.","family":"Vendetti","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1592-2388","authenticated-orcid":true,"given":"Pinakin","family":"Pandya","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Clump","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schamus-Haynes","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meysam","family":"Tavakoli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"diMayorca","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed M.","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jina","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of 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USA."},{"name":"Division of Hematology-Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Bakkenist","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Medicine, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 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