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

被引：478

作者：

Zhang, Yuanyuan ^{[1
]}

Chen, Hongyan ^{[2
]}

Mo, Hongnan ^{[3
]}

Hu, Xueda ^{[1
]}

Gao, Ranran ^{[1
]}

Zhao, Yahui ^{[2
]}

Liu, Baolin ^{[1
]}

Niu, Lijuan ^{[4
]}

Sun, Xiaoying ^{[5
]}

Yu, Xiao ^{[2
]}

Wang, Yong ^{[4
]}

Chang, Qing ^{[4
]}

Gong, Tongyang ^{[2
]}

Guan, Xiuwen ^{[3
]}

Hu, Ting ^{[2
]}

Qian, Tianyi ^{[3
]}

Xu, Binghe ^{[2
,3
]}

Ma, Fei ^{[2
,3
]}

Zhang, Zemin ^{[1
,6
]}

Liu, Zhihua ^{[2
]}

机构：

[1] Peking Univ, Acad Adv Interdisciplinary Studies, Sch Life Sci, Int Canc Inst,BIOPIC,Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Dept Med Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Dept Ultrasound, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China

[5] Canc Hosp HuanXing ChaoYang Dist, Dept Med Oncol, Beijing 100005, Peoples R China

[6] Shenzhen Bay Lab, Inst Canc Res, Shenzhen 518132, Peoples R China

来源：

CANCER CELL | 2021年 / 39卷 / 12期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

B-CELLS; T-CELLS; TUMOR; LANDSCAPE; IMMUNOTHERAPY; CHALLENGES; OPPORTUNITIES; MECHANISMS; GENERATION; SURVIVAL;

D O I：

10.1016/j.ccell.2021.09.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1578 / +

页数：25

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