Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00776-1 |
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| author | Xiaopeng Sun Margaret L. Axelrod Adrienne G. Waks Jingxin Fu Molly DiLullo Eliezer M. Van Allen Sara M. Tolaney Elizabeth A. Mittendorf Yaomin Xu Justin M. Balko |
| author_facet | Xiaopeng Sun Margaret L. Axelrod Adrienne G. Waks Jingxin Fu Molly DiLullo Eliezer M. Van Allen Sara M. Tolaney Elizabeth A. Mittendorf Yaomin Xu Justin M. Balko |
| author_sort | Xiaopeng Sun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-20af0aa9f9a648e4b44524360b832a13 |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-20af0aa9f9a648e4b44524360b832a132025-08-20T04:01:40ZengNature Portfolionpj Breast Cancer2374-46772025-07-011111810.1038/s41523-025-00776-1Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patientsXiaopeng Sun0Margaret L. Axelrod1Adrienne G. Waks2Jingxin Fu3Molly DiLullo4Eliezer M. Van Allen5Sara M. Tolaney6Elizabeth A. Mittendorf7Yaomin Xu8Justin M. Balko9Cancer Biology Program, Vanderbilt UniversityDepartment of Medicine, Washington University in St LouisDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Surgery, Brigham and Women’s HospitalDepartment of Biostatistics, Vanderbilt University Medical CenterDepartment of Medicine, Vanderbilt University Medical CenterAbstract 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.https://doi.org/10.1038/s41523-025-00776-1 |
| spellingShingle | Xiaopeng Sun Margaret L. Axelrod Adrienne G. Waks Jingxin Fu Molly DiLullo Eliezer M. Van Allen Sara M. Tolaney Elizabeth A. Mittendorf Yaomin Xu Justin M. Balko Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients npj Breast Cancer |
| title | Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients |
| title_full | Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients |
| title_fullStr | Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients |
| title_full_unstemmed | Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients |
| title_short | Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients |
| title_sort | dynamic single cell systemic immune responses in immunotherapy treated early stage hr breast cancer patients |
| url | https://doi.org/10.1038/s41523-025-00776-1 |
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