BIOPIC, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, International Cancer Institute, Peking University, Beijing 100871, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Cancer Cell. 2021 Dec 13;39(12):1578-1593.e8. doi: 10.1016/j.ccell.2021.09.010. Epub 2021 Oct 14.
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.
在三阴性乳腺癌（TNBC）中，联合化疗和检查点抑制剂的益处尚不清楚。我们利用单细胞 RNA 和 ATAC 测序来研究 22 例接受紫杉醇或其与抗 PD-L1 阿替利珠单抗联合治疗的晚期 TNBC 患者的免疫细胞动态。我们证明，基线时高水平的 CXCL13 T 细胞与巨噬细胞的促炎特征相关，并可预测联合治疗的有效反应。在有反应的患者中，淋巴组织诱导（LTi）细胞、滤泡 B（Bfoc）细胞、CXCL13 T 细胞和常规 1 型树突状细胞（cDC1）在联合治疗后协同增加，但紫杉醇单药治疗后减少。我们的数据强调了 CXCL13 T 细胞在抗 PD-L1 治疗中的有效性反应中的重要性，并表明紫杉醇方案减少这些细胞可能会影响 TNBC 治疗中伴随阿替利珠单抗的临床结局。
