{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:25:34Z","timestamp":1793381134126,"version":"4.5.0"},"reference-count":64,"publisher":"American Association for Cancer Research (AACR)","issue":"9","funder":[{"name":"NIH NCI","award":["R21CA182614"],"award-info":[{"award-number":["R21CA182614"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14-1-0191"],"award-info":[{"award-number":["W81XWH-14-1-0191"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Immune checkpoint blockade (ICB) therapy, which targets T cell\u2013inhibitory receptors, has revolutionized cancer treatment. Among the breast cancer subtypes, evaluation of ICB has been of greatest interest in triple-negative breast cancer (TNBC) due to its immunogenicity, as evidenced by the presence of tumor-infiltrating lymphocytes and elevated PD-L1 expression relative to other subtypes. TNBC incidence is equally distributed across the age spectrum, affecting 10% to 15% of women in all age groups. Here we report that increased immune dysfunction with age limits ICB efficacy in aged TNBC-bearing mice. The tumor microenvironment in both aged mice and patients with TNBC shows decreased IFN signaling and antigen presentation, suggesting failed innate immune activation with age. Triggering innate immune priming with a STING agonist restored response to ICB in aged mice. Our data implicate age-related immune dysfunction as a mechanism of ICB resistance in mice and suggest potential prognostic utility of assessing IFN-related genes in patients with TNBC receiving ICB therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>These data demonstrate for the first time that age determines the T cell\u2013inflamed phenotype in TNBC and affects response to ICB in mice. Evaluating IFN-related genes from tumor genomic data may aid identification of patients for whom combination therapy including an IFN pathway activator with ICB may be required.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1143<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-18-1454","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T14:15:11Z","timestamp":1560953711000},"page":"1208-1227","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":148,"title":["Interferon Signaling Is Diminished with Age and Is Associated with Immune Checkpoint Blockade Efficacy in Triple-Negative Breast Cancer"],"prefix":"10.1158","volume":"9","author":[{"given":"Jaclyn","family":"Sceneay","sequence":"first","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."},{"name":"2Department of Medicine, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Goreczny","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."},{"name":"2Department of Medicine, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Wilson","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Morrow","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly J.","family":"DeCristo","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."},{"name":"2Department of Medicine, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessalyn M.","family":"Ubellacker","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."},{"name":"2Department of Medicine, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbo","family":"Qin","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."},{"name":"2Department of Medicine, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Laszewski","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-8165","authenticated-orcid":false,"given":"Daniel G.","family":"Stover","sequence":"additional","affiliation":[{"name":"3Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-4634","authenticated-orcid":false,"given":"Victor","family":"Barrera","sequence":"additional","affiliation":[{"name":"4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-7576","authenticated-orcid":false,"given":"John N.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Freedman","sequence":"additional","affiliation":[{"name":"5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"6Breast Oncology Program, Dana-Farber\/Brigham and Women's Cancer Center, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Mittendorf","sequence":"additional","affiliation":[{"name":"6Breast Oncology Program, Dana-Farber\/Brigham and Women's Cancer Center, Boston, Massachusetts."},{"name":"7Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra S.","family":"McAllister","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, 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