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

• Published in: Cancer cell Vol. 39; no. 12; pp. 1578 - 1593.e8
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.12.2021
• Subjects: anti-PD-L1 blockade; atezolizumab in combination with paclitaxel; Female; Humans; immune cells; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Single-Cell Analysis - methods; single-cell RNA-seq and ATACseq; temporal dynamics; Triple Negative Breast Neoplasms - drug therapy; triple-negative breast cancer; immune cells; triple-negative breast cancer; anti-PD-L1 blockade; atezolizumab in combination with paclitaxel; single-cell RNA-seq and ATACseq; temporal dynamics
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccell.2021.09.010

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. [Display omitted] •Dynamic immune cell alterations revealed in TNBC following anti-PD-L1 treatment•CD8-CXCL13 and CD4-CXCL13 T cells predict effective responses to PD-L1 blockade•Proinflammatory macrophages expressing CXCL9 are associated with CXCL13+ T cells•Paclitaxel impairs the expansion of responsive immune cells caused by atezolizumab Zhang et al. combine single-cell RNA-seq, TCR-seq, and ATAC-seq to investigate immune cell dynamics in the tumor microenvironment and peripheral blood of patients with TNBC treated with paclitaxel or paclitaxel plus atezolizumab, revealing immune features of responders and nonresponders, the mechanisms and intertwined effects of paclitaxel and atezolizumab in TNBC treatment.