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，联合化疗与检查点抑制剂的益处还不是很清楚。我们利用单细胞 RNA 和 ATAC 测序来检查 22 名接受紫杉醇或其与抗 PD-L1 atezolizumab 联合治疗的晚期 TNBC 患者的免疫细胞动力学。我们证明高水平的基线 CXCL13 ⁺ T 细胞与巨噬细胞的促炎特征有关，并且可以预测对联合治疗的有效反应。在反应性患者中，淋巴组织诱导 (LTi) 细胞、滤泡 B (Bfoc) 细胞、CXCL13 ⁺T 细胞和常规 1 型树突细胞 (cDC1) 在联合治疗后一致增加，但在紫杉醇单药治疗后减少。我们的数据强调了 CXCL13 ⁺ T 细胞在对抗 PD-L1 疗法的有效反应中的重要性，并表明通过紫杉醇方案减少它们可能会损害伴随 atezolizumab 治疗 TNBC 的临床结果。