Remodeling of T and endothelial cells during total neoadjuvant therapy in rectal cancer
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<sup>+</sup>CD8<sup>+</sup> effector memory T cells with high IFNG expression, potentially contributing to improved complete response rates. The abundance of tumor-infiltrating CD8<sup>+</sup> T cells is correlated with the enrichment of the ACKR1<sup>+</sup> endothelial subset after TNT. We further validated that endothelial cells (ECs), when stimulated by IFNγ, potentially released by CD8<sup>+</sup> T cells, acquire an enhanced ability for presenting antigens and activating CD8<sup>+</sup> T cells. Together, our study systematically characterizes the TME dynamics and uncovers the unique interaction between activated CD8<sup>+</sup> T cells and ECs after TNT.
Authors
- Wei Zhou (ORCID: https://orcid.org/0000-0002-6050-8311)
- Wenhong Hou
- Shijie Hao (ORCID: https://orcid.org/0000-0001-9845-3101)
- Wei-Jian Mei (ORCID: https://orcid.org/0000-0002-0025-2908)
- Sijin Cheng (ORCID: https://orcid.org/0000-0002-2565-7127)
- Qiaoqi Sui (ORCID: https://orcid.org/0000-0001-5191-218X)
- Peirong Ding (ORCID: https://orcid.org/0000-0002-0796-8175)
- Leen Liao
- Fei Tang (ORCID: https://orcid.org/0000-0003-1475-5028)
- Xiao Chen (ORCID: https://orcid.org/0000-0002-4438-5286)
- Kezhuo Yu (ORCID: https://orcid.org/0000-0003-1576-8293)
- Hu‐Nan Sun (ORCID: https://orcid.org/0000-0002-7136-0172)
- Zemin Zhang (ORCID: https://orcid.org/0000-0003-3789-6536)
- Yufei Bo
- Shishang Qin (ORCID: https://orcid.org/0000-0003-0324-5073)
- Xiuqing Zhang (ORCID: https://orcid.org/0000-0003-4578-8359)
- Yujia Jiang
- Lijuan Jiang (ORCID: https://orcid.org/0000-0002-4659-2457)
- Renzhi Wang (ORCID: https://orcid.org/0000-0003-2445-8182)
- Yuhui Miao (ORCID: https://orcid.org/0009-0003-8075-4012)
- Linnan Zhu
- Qianqian Gao (ORCID: https://orcid.org/0000-0001-9858-4187)
- Xinnan Ling
- Dongfang Wang (ORCID: https://orcid.org/0000-0001-5833-0115)
Institutions
- BGI Group (China) (CN)
- Sun Yat-sen University (CN)
- Peking University (CN)
- Shenzhen Bay Laboratory (CN)
- Sun Yat-sen University Cancer Center (CN)
- State Key Laboratory of Chemical Engineering (CN)
- Center for Life Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- BGI Research (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Cancer Cell
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1016/j.ccell.2025.10.008
- Citations
- 2
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 2.09