Longitudinal single-cell profiling of breast tumors of the NeoLetExe trial
To access the single-cell RNA-seq data associated with our publication
“Longitudinal single-cell profiling of breast tumors highlights immune and epigenetic mechanisms associated with sensitivity to aromatase inhibitors”, we provide three options.
- Filtered gene expression count matrices (direct download)
Sample-level filtered gene expression count matrices, processed according to our cell-level quality control (QC) criteria, can be downloaded directly at sparse_scRNA_count_matrix_NeoLetExe - Comprehensive data package at EGA
Sample-level unfiltered gene expression count matrices, sample-level cis-regulatory element count matrices from scRNA-seq, as well as MiXCR output for scTCR and scBCR sequencing, have been deposited in the European Genome-phenome Archive (EGA) under study number EGAS50000001362 - Interactive data exploration (Shiny application)
An interactive Shiny application is available to explore and interrogate the data. This application allows users to visualize gene expression patterns, cell-type annotations, and other features without needing to download or process the datasets locally.
https://tekpli.shinyapps.io/shinyappmulti_neoletexe_scrnaseq/
Summary of the study
Estrogen receptor (ER)-positive breast cancer treatment is primarily based on endocrine therapy.
To dissect mechanisms of sensitivity to aromatase inhibitors in ER-positive breast cancer, we profiled tumor biopsies from 25 patients during neoadjuvant therapy using single-cell RNA sequencing, immune receptor sequencing, and enhancer activity mapping.
Malignant cells with high ER signaling and elevated activity of enhancers with ER binding sites were sensitive to treatment. Resistance was associated with androgen receptor signaling, de-differentiation, and epithelial mesenchymal transition. Poor responders used the androgen receptor cis-regulome under treatment pressure.
The baseline tumor microenvironment was associated with tumor downstaging. Poor responders exhibited a 'hot’, yet ineffective immune landscape enriched for naive lymphoid and undifferentiated myeloid cells. Good responders showed an active immune microenvironment with sustained clonal expansion of T cells.
Our longitudinal single-cell analyses elucidate the genetic, cellular and epigenetic mechanisms driving sensitivity and resistance to neoadjuvant aromatase inhibition in ER positive breast cancer.
Graphical summary
