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Overrepresentation analysis was performed using WebGestalt. All statistical tests were two-sided.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty candidate genes positively correlated (r\u2009\u2265\u20090.4) with AI-resistant proliferation in LumB and were upregulated greater than twofold. Gene ontologies identified that the targetable immune checkpoint (IC) components IDO1, LAG3, and PD1 were overrepresented resistance candidates (P\u2009\u2264\u2009.001). High IDO1 mRNA was associated with poor prognosis in LumB disease (Molecular Taxonomy of Breast Cancer International Consortium, hazard ratio = 1.43, 95% confidence interval = 1.04 to 1.98, P\u2009=\u2009.03). IDO1 also statistically significantly correlated with STAT1 at protein level in LumB disease (Pearson r\u2009=\u20090.74). As a composite immune tolerance signature, expression of IFN-\u03b3\/STAT1 pathway components was associated with higher baseline Ki67, lower estrogen, and progesterone receptor mRNA levels and worse disease-specific survival (P\u2009=\u2009.002). In a tissue microarray analysis, IDO1 was observed in stromal cells and tumor-associated macrophages, with a higher incidence in LumB cases. Furthermore, IDO1 expression was associated with a macrophage mRNA signature (M1 by CIBERSORT Pearson r\u2009=\u20090.62 ) and by tissue microarray analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targetable IC components are upregulated in the majority of endocrine therapy\u2013resistant LumB cases. Our findings provide rationale for IC inhibition in poor-outcome ER-positive breast cancer.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jnci\/djz213","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T20:08:41Z","timestamp":1572293321000},"page":"737-746","source":"Crossref","is-referenced-by-count":61,"title":["Immune Checkpoint Profiles in Luminal B Breast Cancer 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