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Single-Cell Transcriptomics Reveals Immune Landscape Dynamics in Metastatic Hormone Receptor-Positive Breast Cancer
Corinne H Strawser1, Binita Chakraborty2, Daniel Michaud3
1Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio.
Summary
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) impact the tumor immune microenvironment in advanced breast cancer. Treatment altered immune cell gene expression and proportions, affecting patient survival.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Advanced ER+/HER2- breast cancer is typically treated with CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET).
- CDK4/6i are known to induce cell cycle arrest but also modulate the tumor immune microenvironment.
- Understanding these immunomodulatory effects is crucial for optimizing treatment strategies.
Purpose of the Study:
- To characterize the baseline immune landscape in advanced ER+/HER2- breast cancer.
- To investigate the immunomodulatory effects of abemaciclib plus ET on tumor-infiltrating immune cells.
- To correlate immune cell gene signatures with patient survival outcomes.
Main Methods:
- Single-cell RNA-sequencing was performed on CD45-enriched cells from 13 matched-pair advanced/metastatic ER+/HER2- breast tumor biopsies.
- Transcriptomic changes in immune cell populations following abemaciclib and ET treatment were analyzed.
- Immune cell gene signatures were tested for association with survival using public datasets.
Main Results:
- 170,798 cells from various metastatic sites were profiled.
- Interferon response genes were downregulated in T cells; antigen presentation genes were upregulated in TAMs and dendritic cells post-treatment.
- TREM2+ TAM proportions decreased with treatment, and lower TREM2+ TAM signature expression correlated with improved survival.
Conclusions:
- Heterogeneous lymphoid and myeloid subpopulations exist in advanced/metastatic breast tumors.
- These subpopulations are associated with late progression on abemaciclib and ET.
- Specific immune cell signatures correlate with overall survival in breast cancer patients.
