Figure 2 from Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor–Positive Breast Cancer
Year: 2023
Type: other
Abstract: Endocrine treatment shapes tumor immune microenvironment in primary hormone receptor–positive breast cancer. A–F, Digital spatial profiling proteomic levels (log2 expression levels) of immune cell surface markers ranking from highest to lowest expression. A, Baseline levels within the immune regions in tumors from patients who received endocrine therapy [F(11, 312) = 57.1, P < 2e−16, one-way ANOVA]. B, Protein expression levels within the immune regions after 2 weeks of endocrine treatment [F(11, 276) = 41.7, P < 2e−16, one-way ANOVA]. C, Protein expression levels within the immune regions after 24 weeks of endocrine treatment at the time of surgery [F(11, 1212) = 305.2, P < 2e−16, one-way ANOVA]. D, Baseline levels within the invasive epithelial cell regions in tumors from patients who received endocrine therapy [F (11, 732) = 126.3, P < 2e−16, one-way ANOVA]. E, Protein expression levels within the invasive epithelial regions after 2 weeks of endocrine treatment (P < 2e−16, one-way ANOVA). F, Protein expression levels within the invasive epithelial cell regions after 24 weeks of endocrine treatment at the time of surgery (P < 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. G, Trajectory plot of TIL fractions between baseline and 2 weeks. P-val, P value (paired Wilcoxon signed-rank test with continuity correction). H, 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. P-val, P value (paired Wilcoxon signed-rank test with continuity correction). I, GSVA of the T-cell accumulation gene set in primary ER+ breast cancer biopsies from pre- and post-neoadjuvant AI treatment. J, 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. K–M, 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 (y-axis) for signatures of immune-checkpoint blockade (ICB) resistance (K), T-regulatory (Treg) accumulation (L), and cytotoxic T-cell accumulation (M). Comparison between the quartiles was done with a t test. N, number of patients included in the corresponding analysis.
Authors: Francisco Hermida-Prado, Yingtian Xie, Shira Sherman, Zsuzsanna Nagy, Douglas Russo, Tara Akhshi, Zhengtao Chu, Avery Feit, Marco Campisi, Minyue Chen, Agostina Nardone, Cristina Guarducci, Klothilda Lim, Alba Font-Tello, Irene Lee, Juana García-Pedrero, Israel Cañadas, Judith Agudo, Ying Huang, Tal Sella, Qingchun Jin, Nabihah Tayob, Elizabeth A. Mittendorf, Sara M. Tolaney, Xintao Qiu, Henry Long, William F. Symmans, Jia-Ren Lin, Sandro Santagata, Isabelle Bedrosian, Denise A. Yardley, Ingrid A. Mayer, Edward T. Richardson, Giacomo Oliveira, Catherine J. Wu, Eugene F. Schuster, Mitch Dowsett, Alana L. Welm, David Barbie, Otto Metzger, Rinath Jeselsohn
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4387263131