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

Zhang Yuanyuan; Chen Hongyan; Mo HongnanHu XuedaGao RanranZhao YahuiLiu BaolinNiu LijuanSun XiaoyingYu XiaoWang YongChang QingGong TongyangGuan XiuwenHu TingQian TianyiXu BingheMa FeiZhang ZeminLiu Zhihua

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

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

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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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来源
《Cancer Cell》 |2021年第12期|1578-1593|共16页
作者
Zhang Yuanyuan; Chen Hongyan; Mo HongnanHu XuedaGao RanranZhao YahuiLiu BaolinNiu LijuanSun XiaoyingYu XiaoWang YongChang QingGong TongyangGuan XiuwenHu TingQian TianyiXu BingheMa FeiZhang ZeminLiu Zhihua;
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作者单位

State Key Lab Mol Oncol,Chinese Acad Med Sci & Peking Union Med Coll;

Acad Adv Interdisciplinary Studies,Peking Univ;

Dept Ultrasound,Chinese Acad Med Sci & Peking Union Med CollDept Med Oncol,Chinese Acad Med Sci & Peking Union Med CollDept Med Oncol,Canc Hosp HuanXing ChaoYang Dist;

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正文语种英语
中图分类肿瘤学;
关键词
B-CELLS; T-CELLS; TUMOR; LANDSCAPE; IMMUNOTHERAPY; CHALLENGES; OPPORTUNITIES; MECHANISMS; GENERATION; SURVIVAL;

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

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