{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:06:35Z","timestamp":1788872795288,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573661"],"award-info":[{"award-number":["82573661"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002418","name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College","doi-asserted-by":"publisher","award":["Chmdf2024\u2010xrzx09\u201014"],"award-info":[{"award-number":["Chmdf2024\u2010xrzx09\u201014"]}],"id":[{"id":"10.13039\/501100002418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Immune checkpoint blockade (ICB) has improved outcomes for patients with triple\u2010negative breast cancer (TNBC), yet resistance remains widespread and its molecular basis is not fully understood. Through single\u2010cell RNA sequencing (scRNA\u2010seq) of paired pre\u2010 and post\u2010treatment tumor samples from patients who failed to achieve pathological complete response (non\u2010pCR) after neoadjuvant PD\u20101 therapy, we identified a marked upregulation of interleukin\u201027 receptor subunit alpha (IL27RA) in malignant epithelial cells within residual lesions. Integration with scRNA\u2010seq profiles from an independent cohort of three pCR patients showed that this\n                    <jats:italic>IL27RA<\/jats:italic>\n                    upregulation in malignant epithelium is largely restricted to non\u2010pCR residual tumors, and high IL27RA expression correlated with poor survival in TNBC cohorts. Mechanistically, IL27RA suppresses MHC\u2010I expression by activating the PI3K\/AKT pathway\u2014rather than the classical IL\u201027\/STAT axis\u2014thereby impairing CD8\u207a T\u2010cell cytotoxic function. Inhibition of AKT reversed this phenotype and restored antigen\u2010specific killing. In orthotopic tumor models, mimicking systemic loss of\n                    <jats:italic>Il27ra<\/jats:italic>\n                    significantly reduced tumor growth and prolonged survival in immunocompetent mice, with single\u2010cell profiling indicating enhanced intratumoral T\u2010cell and NK\u2010cell effector activity. Collectively, our findings identify an epithelial\u2010intrinsic IL27RA\u2013PI3K\/AKT\u2013MHC\u2010I axis as a central driver of immune evasion and ICB resistance in TNBC and support IL27RA as a promising therapeutic target for overcoming immunotherapy resistance.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516703","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:16:46Z","timestamp":1767586606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting IL27RA Enhances Immunotherapy in Triple\u2010Negative Breast Cancer by Modulating Tumor Cells and the Tumor Microenvironment"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiachi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of General Surgery the Second Xiangya Hospital of Central South University  Changsha 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