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Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients
Xiaopeng Sun1, Margaret L Axelrod2, Adrienne G Waks3
1Cancer Biology Program, Vanderbilt University, Nashville, TN, USA.
Abstract:
The limited added benefit of immune checkpoint inhibitors in breast cancer indicates the pressing need to identify biomarkers of response to minimize risk and maximize benefit. We used single cell RNA sequencing and T cell receptor (TCR) sequencing of peripheral blood mononuclear cells (for 28 samples comprising 79,284 cells) to monitor the peripheral immune dynamic of an exploratory cohort of hormone receptor positive breast cancer patients treated with neoadjuvant nab-paclitaxel+pembrolizumab with the ultimate goal of identifying potential peripheral blood predictive biomarkers. In responsive patients, Granzyme B positive (GZMB+) cytotoxic CD8 T cells expanded post-nab-paclitaxel+pembrolizumab, accompanied by rapid changes in TCR clones. In contrast, non-responders' peripheral T cells may experience terminal exhaustion and are not significantly altered by treatment. In addition, B cell and monocyte-specific interferon response signatures were also associated with response. Our data suggests that peripheral immunological signatures may represent a facile way to monitor dynamic antitumor immune response.
Insights
Peripheral immune cell changes, including cytotoxic CD8 T cells and interferon responses in B cells and monocytes, can predict treatment effectiveness in hormone receptor-positive breast cancer patients receiving neoadjuvant nab-paclitaxel plus pembrolizumab.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) show limited benefit in breast cancer, necessitating biomarkers for personalized treatment.
- Identifying predictive biomarkers is crucial to optimize therapy for hormone receptor-positive breast cancer patients.
Purpose of the Study:
- To identify peripheral blood predictive biomarkers for response to neoadjuvant nab-paclitaxel plus pembrolizumab in breast cancer.
- To monitor peripheral immune dynamics during neoadjuvant therapy.
Main Methods:
- Single-cell RNA sequencing and T cell receptor (TCR) sequencing of peripheral blood mononuclear cells from 28 patients.
- Analysis of immune cell populations and their functional states.
Main Results:
- Responsive patients showed expansion of Granzyme B-positive (GZMB+) cytotoxic CD8 T cells and TCR clone changes post-treatment.
- Non-responders exhibited signs of T cell exhaustion with minimal treatment-induced alterations.
- Interferon response signatures in B cells and monocytes correlated with treatment response.
Conclusions:
- Peripheral immunological signatures can serve as accessible indicators of dynamic antitumor immune responses.
- These findings may facilitate monitoring treatment efficacy and guiding therapeutic decisions in breast cancer.
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