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

Y Zhang, H Chen, H Mo, X Hu, R Gao, Y Zhao, B Liu… - Cancer cell, 2021 - cell.com
Y Zhang, H Chen, H Mo, X Hu, R Gao, Y Zhao, B Liu, L Niu, X Sun, X Yu, Y Wang, Q Chang…
Cancer cell, 2021cell.com
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 …
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.
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