北京大学张泽民团队近日取得一项新成果。经过不懈努力，他们开发出直肠癌新辅助治疗中T细胞和内皮细胞的重塑。相关论文于2025年11月6日发表在《癌细胞》杂志上。

利用单细胞RNA、T细胞受体和治疗前后匹配样本的空间转录组测序，该课题组研究人员描述了不同新辅助治疗诱导的肿瘤微环境（TME）动态。TNT与减少的调节性T细胞和增加IFNG⁺CD8⁺效应记忆T细胞相关，IFNG高表达，可能有助于提高完全缓解率。肿瘤浸润性CD8⁺ T细胞的丰度与TNT后ACKR1⁺内皮亚群的富集相关。该课题组进一步证实内皮细胞（ECs）在受到IFNγ刺激时，获得了增强的递呈抗原和激活CD8⁺ T细胞的能力，IFNγ可能由CD8⁺ T细胞释放。总之，他们的研究系统地表征了TME动力学，并揭示了TNT后活化的CD8⁺ T细胞与ECs之间独特的相互作用。

据悉，全面新辅助治疗（TNT）是局部晚期直肠癌（LARC）的标准治疗方法，但其疗效背后的免疫重塑机制尚不清楚。

附：英文原文

Title: Remodeling of T and endothelial cells during total neoadjuvant therapy in rectal cancer

Author: Qianqian Gao, Xinnan Ling, Leen Liao, Fei Tang, Yujia Jiang, Shishang Qin, Wenhong Hou, Wei Zhou, Lijuan Jiang, Chunman Xiao, Yufei Bo, Yuhui Miao, Hai-xi Sun, Ruoyao Wang, Kezhuo Yu, Qiaoqi Sui, Shijie Hao, Weijian Mei, Dongfang Wang, Xiuqing Zhang, Sijin Cheng, Linnan Zhu, Peirong Ding, Zemin Zhang

Issue&Volume: 2025-11-06

Abstract: 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.

DOI: 10.1016/j.ccell.2025.10.008

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00449-0