{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:08:41Z","timestamp":1779170921097,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying reliable biomarkers for immunotherapy response remains challenging. Solute carrier family 7 member 11 (SLC7A11), a key regulator of redox homeostasis and ferroptosis, demonstrates significant tumor-promoting potential across cancers, yet its pan-cancer associations with immunotherapy-related features and interaction with microRNAs in triple-negative breast cancer pathogenesis remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically analyzed SLC7A11 expression across cancer types using TCGA and GTEx data, and evaluated its associations with immunotherapy-related features. Survival analyses were assessed in general and immunotherapy-treated cohorts. A miRNA regulatory network targeting SLC7A11 was constructed in breast cancer and the SLC7A11-miR-148b-3p axis was tested via\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments in triple-negative breast cancer (TNBC) cell models (MDA-MB-231 and MDA-MB-468).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pan-cancer analysis revealed upregulation of SLC7A11 transcriptional expression in over 88% tumor types, and associations with established immunotherapy-related features, including tumor mutational burden, microsatellite instability, PD-L1 expression, and immune infiltration. Higher SLC7A11 expression was associated with improved response to immunotherapy, but inferior prognosis in most tumors, including breast cancer. In TNBC cell models,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments supported that miR-148b-3p negatively regulated SLC7A11, and higher SLC7A11 expression was associated with increased glutathione levels, reduced lipid peroxidation, and enhanced cell survival under ferroptosis-inducing conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our pan-cancer analyses reveal a potential biological link between SLC7A11, ferroptosis, and tumor immunity, generating the hypothesis that SLC7A11 may serve as a biomarker for immune checkpoint inhibitor response. In TNBC models, we identify the miR-148b-3p\/SLC7A11 axis as a potential regulator of ferroptosis resistance based on\n                      <jats:italic>in vitro<\/jats:italic>\n                      findings, warranting further\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1752767","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:41:38Z","timestamp":1779169298000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An integrated analysis of SLC7A11 as a pan-cancer immunotherapeutic biomarker with experimental validation of its regulation by miR-148b-3p in breast cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Songchen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Zheng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guannan","family":"Ma","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Digital Technology in Medical Diagnostics","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaifeng","family":"Niu","sequence":"additional","affiliation":[{"name":"China National Center for Bioinformation","place":["Beijing, China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital 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