{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:55:17Z","timestamp":1793832917143,"version":"4.6.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"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>Triple-negative breast cancer (TNBC) is a heterogeneous disease lacking approved targeted therapies and standardized treatment regimens. Among its molecular subtypes, luminal androgen receptor-positive (LAR+) TNBC is characterized by reduced proliferative activity and a lower sensitivity to chemotherapy. The tumor immune microenvironment (TIME) plays a critical role in shaping treatment responses; however, its spatial organization and cellular composition in LAR+ TNBC remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this exploratory study, we performed multiplex immunofluorescence analysis to characterize 18 immune and tumor cell subtypes in paired pre- and post-neoadjuvant therapy (NAT) samples from small, exploratory cohort of patients with LAR+ TNBC, stratified by pathological complete response (pCR). We assessed immune cell composition, expression of exhaustion markers, and spatial relationships among cellular populations to explore TIME features associated with different pathological responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients who achieved pCR displayed higher pre-treatment densities of specific immune subsets, including CD20\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      , CD4\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      , and CD8\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      TIM3\n                      <jats:sup>+<\/jats:sup>\n                      cells, consistent with an immune-enriched microenvironment. Spatial analyses revealed distinct patterns between Responders (Resp) and Non-Responders (NoResp). In Resp, tumor cells (PANCK\n                      <jats:sup>+<\/jats:sup>\n                      ) were initially located closer to PD-L1\u2013expressing tumor cells (PANCK\n                      <jats:sup>+<\/jats:sup>\n                      PD-L1\n                      <jats:sup>+<\/jats:sup>\n                      ), with this proximity decreasing after NAT. In contrast, in non-Resp, immunosuppressive tumor cells moved closer to tumor cells following treatment. Moreover, NAT in Resp was associated with a spatial repositioning of CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells toward tumor cells. B cells and regulatory B cells (Bregs) also exhibited differential spatial dynamics between the two groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory analysis describes distinct immune compositions and spatial arrangements of the TIME in LAR+ TNBC. Our findings suggest that specific immune enrichments and spatial remodeling patterns may differ between patients with different pathological outcomes, whereas the persistence of immunosuppressive niches characterizes non-Resp. Given the small sample size and the inclusion of immune checkpoint inhibitors in a subset of patients, all of whom achieved pCR, these observations should be considered strictly hypothesis-generating. Larger and more homogeneous cohorts will be required to validate these findings and to determine their potential clinical relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1810096","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:08:59Z","timestamp":1779430139000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial organization of the tumor immune microenvironment in LAR+ triple-negative breast cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Donatella","family":"Lucchetti","sequence":"first","affiliation":[{"name":"Multiplex Spatial Profiling Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario \u2018Agostino Gemelli\u2019 IRCCS","place":["Rome, Italy"]},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Di Leone","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Breast Unit, Department of Woman and Child Health and Public Health, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]},{"name":"Santoro Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS","place":["Rome, Italy"]},{"name":"Pathology Institute, Catholic University of Sacred Heart","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Sabbatinelli","sequence":"additional","affiliation":[{"name":"National Facility for Genomics, Human Technopole, Viale Rita Levi-Montalcini 1","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Toma","sequence":"additional","affiliation":[{"name":"Multiplex Spatial Profiling Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario \u2018Agostino Gemelli\u2019 IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Antonio","sequence":"additional","affiliation":[{"name":"Breast Unit, Department Of Woman And Child\u2019s Health And Public Health, Fondazione Policlinico Universitario A. 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