直肠癌全程新辅助治疗期间 T 细胞和内皮细胞的重塑

Total neoadjuvant therapy (TNT) is a standard care for locally advanced rectal cancer (LARC), yet the immune remodeling mechanisms underlying its efficacy remain unclear. Using single-cell RNA, T cell receptor, and spatial transcriptome sequencing of matched pre- and post-treatment samples, we depicted the tumor microenvironment (TME) dynamics induced by different neoadjuvant therapies.

TNT is associated with reduced regulatory T cells and increased IFNG + CD8 + effector memory T cells with high IFNG expression, potentially contributing to improved complete response rates. The abundance of tumor-infiltrating CD8 + T cells is correlated with the enrichment of the ACKR1 + endothelial subset after TNT.

We further validated that endothelial cells (ECs), when stimulated by IFNγ, potentially released by CD8 + T cells, acquire an enhanced ability for presenting antigens and activating CD8 + T cells.

Together, our study systematically characterizes the TME dynamics and uncovers the unique interaction between activated CD8 + T cells and ECs after TNT.