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The androgen receptor gene (\n                      <jats:italic>AR<\/jats:italic>\n                      ), expressed in a substantial proportion of ER-positive tumors, has been implicated in tumor biology; however, its role in the tumor immune microenvironment and immunotherapy response is not well understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the association between\n                      <jats:italic>AR<\/jats:italic>\n                      expression, transcriptome-derived immune cell-associated signatures, and response to ICIs in 4046 patients with breast cancer across five cohorts with bulk transcriptomic data and two cohorts with single-cell transcriptomic data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High\n                      <jats:italic>AR<\/jats:italic>\n                      expression was consistently associated with reduced transcriptome-derived tumor-infiltrating leukocyte scores across multiple ER+\/HER2- cohorts. Specifically, signatures associated with cluster of differentiation (CD)-8+ T-cell subsets, dendritic cells, and M1 macrophages were significantly reduced in\n                      <jats:italic>AR<\/jats:italic>\n                      -high tumors, indicating a transcriptionally immune-suppressed tumor microenvironment. In the I-SPY2 cohort,\n                      <jats:italic>AR<\/jats:italic>\n                      -high tumors demonstrated significantly lower pathological complete response rates after neoadjuvant ICI therapy. Furthermore,\n                      <jats:italic>AR<\/jats:italic>\n                      expression showed a predictive performance for ICI response that was superior to that with\n                      <jats:italic>programmed cell death protein-1<\/jats:italic>\n                      and\n                      <jats:italic>programmed cell death ligand-1<\/jats:italic>\n                      (area under the curve 0.82 vs. 0.73 and 0.60, respectively). Interestingly, single-cell analysis revealed that\n                      <jats:italic>AR<\/jats:italic>\n                      expression across multiple cell types, including epithelial, endothelial, and myeloid, was associated with reduced ICI responsiveness. Additionally,\n                      <jats:italic>AR<\/jats:italic>\n                      inhibition using enzalutamide was associated with increased signatures associated with CD8+ T cells, dendritic cells, and M1 macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that\n                      <jats:italic>AR<\/jats:italic>\n                      expression is associated with an immunosuppressive tumor microenvironment and reduced response to ICIs in ER+\/HER2- breast cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1245\/s10434-026-20685-2","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:55:11Z","timestamp":1792508111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Androgen Receptor (AR) Expression is Associated with an Immune-Cold Phenotype and Reduced Response to Immune Checkpoint Inhibitors in ER-Positive\/HER2-Negative Breast Cancer"],"prefix":"10.1245","author":[{"given":"Jun","family":"Arima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Chida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Shima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kuramoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Hamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunairah","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Hakamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seita","family":"Hagihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiko","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Woong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6435-4241","authenticated-orcid":false,"given":"Kazuaki","family":"Takabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"20685_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.674192","volume":"12","author":"J Goldberg","year":"2021","unstructured":"Goldberg J, Pastorello RG, Vallius T, et al. 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