Summary

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.

Overall design

The mechanism underlying combination therapy of paclitaxel plus atezolizumab in advanced TNBC is poorly understood. Using single-cell RNA-seq and ATAC-seq technologies, we generated transcriptomes and chromatin accessibility profiles of CD45+ immune cells from primary or metastatic tumor tissues and peripheral blood of 22 advanced TNBC patients treated with paclitaxel or its combination with atezolizumab.

Contributors

Yuanyuan Zhang†, Hongyan Chen†, Hongnan Mo†, Xueda Hu†, Binghe Xu✉️, Fei Ma✉️, Zemin Zhang✉️, Zhihua Liu✉️

Contact

xubinghe@csco.org.cn (Binghe Xu), drmafei@126.com (Fei Ma), zemin@pku.edu.cn (Zemin Zhang), liuzh@cicams.ac.cn (Zhihua Liu)