{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:14:06Z","timestamp":1792012446516,"version":"4.4.0"},"reference-count":53,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,5,31]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied mouse strain, C57BL\/6, is also the only one for which multiple genetic variants are available to facilitate the exploration of the cancer-immunity dialog. Driven by the fact that no hormone receptor-positive (HR<jats:sup>+<\/jats:sup>) C57BL\/6-derived mammary carcinoma cell lines are available, we decided to establish such cell lines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>BC was induced in female C57BL\/6 mice using a synthetic progesterone analog (medroxyprogesterone acetate, MPA) combined with a DNA damaging agent (7,12-dimethylbenz[a]anthracene, DMBA). Cell lines were established from these tumors and selected for dual (estrogen+progesterone) receptor positivity, as well as transplantability into C57BL\/6 immunocompetent females.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One cell line, which we called B6BC, fulfilled these criteria and allowed for the establishment of invasive estrogen receptor-positive (ER<jats:sup>+<\/jats:sup>) tumors with features of epithelial to mesenchymal transition that were abundantly infiltrated by myeloid immune populations but scarcely by T lymphocytes, as determined by single-nucleus RNA sequencing and high-dimensional leukocyte profiling. Such tumors failed to respond to programmed cell death-1 (PD-1) blockade, but reduced their growth on treatment with ER antagonists, as well as with anthracycline-based chemotherapy, which was not influenced by T-cell depletion. Moreover, B6BC-derived tumors reduced their growth on CD11b blockade, indicating tumor sustainment by myeloid cells. The immune environment and treatment responses recapitulated by B6BC-derived tumors diverged from those of ER<jats:sup>+<\/jats:sup> TS\/A cell-derived tumors in BALB\/C mice, and of ER<jats:sup>\u2013<\/jats:sup> E0771 cell-derived and MPA\/DMBA-induced tumors in C57BL\/6 mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>B6BC is the first transplantable HR<jats:sup>+<\/jats:sup> BC cell line derived from C57BL\/6 mice and B6BC-derived tumors recapitulate the complex tumor microenvironment of locally advanced HR<jats:sup>+<\/jats:sup> BC naturally resistant to PD-1 immunotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-007117","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T09:41:07Z","timestamp":1687340467000},"page":"e007117","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma"],"prefix":"10.1136","volume":"11","author":[{"given":"Maria","family":"Perez-Lanzon","sequence":"first","affiliation":[{"name":"Team \"Metabolism, Cancer & Immunity\", Centre de Recherche des Cordeliers, UMRS 1138, Inserm, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Paris, France"},{"name":"Gustave Roussy Institute, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Carbonnier","sequence":"additional","affiliation":[{"name":"Team \"Metabolism, Cancer & Immunity\", Centre de Recherche des Cordeliers, UMRS 1138, Inserm, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Paris, France"},{"name":"Gustave Roussy Institute, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Cordier","sequence":"additional","affiliation":[{"name":"Team \u2018Proliferation, Stress and Liver Physiopathology\u2019, Centre de Recherche des Cordeliers, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Domenica Elisa","family":"De Palma","sequence":"additional","affiliation":[{"name":"Team \"Metabolism, Cancer & Immunity\", Centre de Recherche des Cordeliers, UMRS 1138, Inserm, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Paris, France"},{"name":"Gustave Roussy Institute, Villejuif, France"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Petrazzuolo","sequence":"additional","affiliation":[{"name":"Team \"Metabolism, Cancer & Immunity\", Centre de Recherche des Cordeliers, UMRS 1138, Inserm, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Paris, France"},{"name":"Gustave Roussy Institute, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Klein","sequence":"additional","affiliation":[{"name":"Centre d'Histologie, d'Imagerie cellulaire et de Cytom\u00e9trie (CHIC), Centre de Recherche des Cordeliers, Paris, France, UMRS1138, Inserm, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriane","family":"Arbaretaz","sequence":"additional","affiliation":[{"name":"Centre d'Histologie, d'Imagerie cellulaire et de Cytom\u00e9trie (CHIC), Centre de Recherche des Cordeliers, Paris, France, 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