Figure 2 from Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor–Positive Breast Cancer
Authors: Hermida-Prado Francisco , Xie Yingtian , Sherman Shira , Nagy Zsuzsanna , Russo Douglas , Akhshi Tara , Chu Zhengtao , Feit Avery , Campisi Marco , Chen Minyue , Nardone Agostina , Guarducci Cristina , Lim Klothilda , Font-Tello Alba , Lee Irene , García-Pedrero Juana , Cañadas Israel , Agudo Judith , Huang Ying , Sella Tal , Jin Qingchun , Tayob Nabihah , Mittendorf Elizabeth A. , Tolaney Sara M. , Qiu Xintao , Long Henry , Symmans William F. , Lin Jia-Ren , Santagata Sandro , Bedrosian Isabelle , Yardley Denise A. , Mayer Ingrid A. , Richardson Edward T. , Oliveira Giacomo , Wu Catherine J. , Schuster Eugene F. , Dowsett Mitch , Welm Alana L. , Barbie David , Metzger Otto , Jeselsohn Rinath 
Published: October 2023

<p>Endocrine treatment shapes tumor immune microenvironment in primary hormone receptor–positive breast cancer. <b>A–F,</b> Digital spatial profiling proteomic levels (log<sub>2</sub> expression levels) of immune cell surface markers ranking from highest to lowest expression. <b>A,</b> Baseline levels within the immune regions in tumors from patients who received endocrine therapy [F(<a href="#bib11" target="_blank">11</a>, 312) = 57.1, <i>P</i> < 2e−16, one-way ANOVA]. <b>B,</b> Protein expression levels within the immune regions after 2 weeks of endocrine treatment [F(<a href="#bib11" target="_blank">11</a>, 276) = 41.7, <i>P</i> < 2e−16, one-way ANOVA]. <b>C,</b> Protein expression levels within the immune regions after 24 weeks of endocrine treatment at the time of surgery [F(<a href="#bib11" target="_blank">11, 1212</a>) = 305.2, <i>P</i> < 2e−16, one-way ANOVA]. <b>D,</b> Baseline levels within the invasive epithelial cell regions in tumors from patients who received endocrine therapy [F (<a href="#bib11" target="_blank">11</a>, 732) = 126.3, <i>P</i> < 2e−16, one-way ANOVA]. <b>E,</b> Protein expression levels within the invasive epithelial regions after 2 weeks of endocrine treatment (<i>P</i> < 2e−16, one-way ANOVA). <b>F,</b> Protein expression levels within the invasive epithelial cell regions after 24 weeks of endocrine treatment at the time of surgery (<i>P</i> < 2e−16, one-way ANOVA). Boxplots show median, 25th, and 75th percentiles as boxes, the minimum of the 75th percentile + 1.5 × IQR, and the maximum observation as the upper whisker and the maximum of the 25th percentile −1.5 × IQR and the minimum observation as the lower whisker. <b>G,</b> Trajectory plot of TIL fractions between baseline and 2 weeks. <i>P</i>-val, <i>P</i> value (paired Wilcoxon signed-rank test with continuity correction). <b>H,</b> Trajectory plot of TIL fractions between 2 weeks and surgery for all patients given endocrine treatment that have TIL observations at all three time points. Each trajectory corresponds to a single patient. <i>P</i>-val, <i>P</i> value (paired Wilcoxon signed-rank test with continuity correction). <b>I,</b> GSVA of the T-cell accumulation gene set in primary ER<sup>+</sup> breast cancer biopsies from pre- and post-neoadjuvant AI treatment. <b>J,</b> Enrichment plot of the top-ranked gene set (estrogen response) enriched in the ESR1 highest (fourth quartile) versus ESR1 lowest (first quartile) ER–positive breast cancer samples from the TCGA cohort. <b>K–M,</b> GSVA of RNA-seq from the ER–positive breast cancer samples from TCGA divided into quartiles based on ESR1 mRNA levels testing the enrichment score (<i>y</i>-axis) for signatures of immune-checkpoint blockade (ICB) resistance (<b>K</b>), T-regulatory (Treg) accumulation (<b>L</b>), and cytotoxic T-cell accumulation (<b>M</b>). Comparison between the quartiles was done with a <i>t</i> test. <i>N</i>, number of patients included in the corresponding analysis.</p>