结直肠癌免疫治疗不同应答背后细胞动力学的时空单细胞分析解析

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.