扩大免疫检查点阻断（ICB）在结直肠癌（CRC）中的疗效迫切需要全面了解治疗反应。在这里，我们分析了 22 名接受 PD-1 阻断的患者的多个连续单细胞样本，以绘制 CRC 患者局部和全身免疫的演变图。在肿瘤中，我们发现了表现出不同反应关联的协调细胞程序。具体而言，耗竭的 T (Tex) 或肿瘤反应性样 CD8 T (Ttr-like) 细胞与治疗效果密切相关，并且在 PD-1 阻断后，Tex 细胞与多种其他肿瘤富集细胞类型显示出相关的比例变化。此外，我们揭示了肿瘤中血液相关 Ttr 样细胞的较少耗尽表型，并发现它们的丰度较高表明治疗结果更好。最后，基线时循环 CD8 T 细胞中较高的主要组织相容性复合体 (MHC) II 相关特征与优异的反应相关。我们的研究提供了对 CRC 新辅助 PD-1 阻断后时空细胞动力学的见解。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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 single-cell 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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.