%0 Journal Article
%T Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer.
%A Chen Y
%A Wang D
%A Li Y
%A Qi L
%A Si W
%A Bo Y
%A Chen X
%A Ye Z
%A Fan H
%A Liu B
%A Liu C
%A Zhang L
%A Zhang X
%A Li Z
%A Zhu L
%A Wu A
%A Zhang Z
%J Cancer Cell
%V 42
%N 7
%D 2024 Jul 8
%M 38981439
%F 38.585
%R 10.1016/j.ccell.2024.06.009
%X 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.