Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer

被引：43

作者：

Chen, Yuqing ^{[1
,2
]}

Wang, Dongfang ^{[1
,2
]}

Li, Yingjie ^{[3
]}

Qi, Lu ^{[4
]}

Si, Wen ^{[1
,2
]}

Bo, Yufei ^{[1
,2
]}

Chen, Xueyan ^{[1
,2
]}

Ye, Zhaochen ^{[1
,2
]}

Fan, Hongtao ^{[1
,2
]}

Liu, Baolin ^{[1
,2
]}

Liu, Chang ^{[1
,2
]}

Zhang, Li ^{[5
]}

Zhang, Xiaoyan ^{[6
]}

Li, Zhongwu ^{[5
]}

Zhu, Linna ^{[1
,2
]}

Wu, Aiwen ^{[3
]}

Zhang, Zemin ^{[1
,2
]}

机构：

[1] Peking Univ, Biomed Pioneering Innovat Ctr BIOP, Beijing 100871, Peoples R China

[2] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China

[3] Peking Univ Canc Hosp & Inst, Gastrointestinal Canc Ctr, State Key Lab Holist Integrat Management Gastroin, Unit 3,Beijing Key Lab Carcinogenesis Translat Re, Beijing 100142, Peoples R China

[4] Changping Lab, Yard 28,Sci Pk Rd, Beijing, Peoples R China

[5] Peking Univ Canc Hosp & Inst, Dept Pathol, Beijing Key Lab Carcinogenesis & Translat Res, State Key Lab Holist Integrat Management Gastroin, Beijing 100142, Peoples R China

[6] Peking Univ Canc Hosp & Inst, Dept Radiol, Beijing Key Lab Carcinogenesis & Translat Res, State Key Lab Holist Integrat Management Gastroin, Beijing 100142, Peoples R China

来源：

CANCER CELL | 2024年 / 42卷 / 07期

基金：

中国国家自然科学基金;

关键词：

REACTIVE T-CELLS; IMMUNE CELLS; BLOCKADE; TUMORS;

D O I：

10.1016/j.ccell.2024.06.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential singlecell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8 + T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8 + T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC.

引用

页码：1268 / 1285.e7

页数：26

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