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We analyzed pre- and on-treatment biopsies from patients with HR\n                    <jats:sup>+<\/jats:sup>\n                    breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor\u2013infiltrating lymphocytes, assessed by H&amp;E staining, and immune-related gene sets, including IFN-\u03b3 signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of\n                    <jats:italic>CXCL9<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL10<\/jats:italic>\n                    , and\n                    <jats:italic>CXCL11<\/jats:italic>\n                    \u2014 chemokine genes involved in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell recruitment \u2014 and the\n                    <jats:italic>CXCR3<\/jats:italic>\n                    receptor were upregulated both before and after letrozole treatment. CXCL11 levels were higher in conditioned media from HR\n                    <jats:sup>+<\/jats:sup>\n                    breast cancer cells cocultured with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Both recombinant CXCL11 and coculture with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells promoted MCF7 and T47D cell growth in estrogen-free conditions. Finally, deletion combined with silencing of the CXCL11 receptors CXCR3 and CXCR7 in MCF7 cells impaired proliferation in response to exogenous CXCL11 and to coculture with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in estrogen-free conditions. These findings suggest that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013associated CXCL11 in the TIME modulated the response of HR\n                    <jats:sup>+<\/jats:sup>\n                    breast cancer cells to estrogen suppression.\n                  <\/jats:p>","DOI":"10.1172\/jci188458","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T17:00:27Z","timestamp":1765299627000},"source":"Crossref","is-referenced-by-count":5,"title":["CD8+ T cells in the tumor microenvironment modulate the response to endocrine therapy in breast cancer"],"prefix":"10.1172","volume":"136","author":[{"given":"Fabiana","family":"Napolitano","sequence":"first","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."},{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunguan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, USA."},{"name":"Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhivya R.","family":"Sudhan","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-6963","authenticated-orcid":true,"given":"Paula I.","family":"Gonzalez-Ericsson","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Unni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahbano","family":"Shakeel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Z.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O\u2019Donnell Jr. School of Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushi","family":"Ahuja","sequence":"additional","affiliation":[{"name":"Lyda Hill Department of Bioinformatics, UTSW Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Guo","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O\u2019Donnell Jr. School of Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Rosario","family":"Chica-Parrado","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Luna","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Ching A.","family":"Lin","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Uemoto","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, 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