Cited by 792Cancer Immunotherapy and BiomarkersBreast Cancer Treatment StudiesImmune cells in cancer

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Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer

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Zhang, Yuanyuan, Chen, Hongyan, Mo, Hongnan, Hu, Xueda, Gao, Ranran, Zhao, Yahui, Liu, Baolin, Niu, Lijuan, Sun, Xiaoying, Yu, Xiao, Wang, Yong, Chang, Qing, Gong, Tongyang, Guan, Xiuwen, Hu, Ting, Qian, Tianyi, Xu, Binghe, Ma, Fei, Zhang, Zemin, Liu, Zhihua·2021·Cancer Cell

DOI 10.1016/j.ccell.2021.09.010

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Abstract

In triple-negative breast cancer (TNBC), the benefit of combining chemotherapy with checkpoint inhibitors is still not very clear. We utilize single-cell RNA- and ATAC-sequencing to examine the immune cell dynamics in 22 patients with advanced TNBC treated with paclitaxel or its combination with the anti-PD-L1 atezolizumab. We demonstrate that high levels of baseline CXCL13 + T cells are linked to the proinflammatory features of macrophages and can predict effective responses to the combination therapy. In responsive patients, lymphoid tissue inducer (LTi) cells, follicular B (Bfoc) cells, CXCL13 + T cells, and conventional type 1 dendritic cells (cDC1) concertedly increase following the combination therapy, but instead decrease after paclitaxel monotherapy. Our data highlight the importance of CXCL13 + T cells in effective responses to anti-PD-L1 therapies and suggest that their reduction by paclitaxel regimen may compromise the clinical outcomes of accompanying atezolizumab for TNBC treatment.

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Authors: Zhang, Y., Chen, H., Mo, H., Hu, X., Gao, R., Zhao, Y., Liu, B., Niu, L., Sun, X., Yu, X., Wang, Y., Chang, Q., Gong, T., Guan, X., Hu, T., Qian, T., Xu, B., Ma, F., Zhang, Z., & Liu, Z.
Affiliations: Peking University (CN)
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Cancer Hospital of Huanxing Chaoyang District Beijing (CN)
Corresponding author: Xu, Binghe
Ma, Fei
Zhang, Zemin
Liu, Zhihua
ORCID: Zhang, Yuanyuan
Chen, Hongyan
Mo, Hongnan
Hu, Xueda
Gao, Ranran
Zhao, Yahui
Liu, Baolin
Niu, Lijuan
Sun, Xiaoying
Yu, Xiao
Wang, Yong
Chang, Qing
Gong, Tongyang
Qian, Tianyi
Xu, Binghe
Ma, Fei
Zhang, Zemin
Liu, Zhihua
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2021-12
Volume: 39
Issue: 12
Pages: 1578-1593.e8
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccell.2021.09.010
OpenAlex: W3205385275
Cited by: 783
References: 77
Citations by year: 2026: 135 · 2025: 206 · 2024: 183 · 2023: 158 · 2022: 93 · 2021: 8
FWCI: 41.16
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Cancer Cell (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (31991171, 81988101, 82030089, 91942307)
Chinese Academy of Meteorological Sciences (2016-I2M-1-001, 2017-I2M-3-004, 2019-I2M-1-003)
Peking University
Beijing Municipal Science and Technology Commission (Z201100005320014)
National Key Research and Development Program of China (2018YFC1312101, 2020YFA0803300)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: triple-negative breast cancer, PD-L1 blockade, atezolizumab, paclitaxel, immune cell dynamics, lymphoid tissue inducer cells, follicular B cells, conventional type 1 dendritic cells, single-cell RNA sequencing, single-cell ATAC-seq
MeSH terms: Immune Checkpoint Inhibitors, Female, Humans, Single-Cell Analysis, Triple Negative Breast Neoplasms

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Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer

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