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

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

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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Species: human
Number of cells: 489490
Number of downloads: 17
Study size: 7GB
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Triple-negative breast cancer