Tumor-draining lymph nodes respond to immune checkpoint inhibition and orchestrate tumor immune remodeling

作者：Jinzhu Zhang, Jianhua Ma, Yaru Niu, Jialiang Liu, Zhexue Wang, Jinyuan Guo, Yongsheng Meng, Ruifang Sun, Zhen Zhang, Haiyi Liu, Juan Xu, L K Zan, Xu Guan, Xishan Wang · 发表于：Cancer Immunology Immunotherapy · 年份：2025 · DOI：10.1007/s00262-025-04187-w · 被引用次数：5 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Immune cells in cancer

BACKGROUND: Immune checkpoint inhibitors have traditionally been understood to exert their effects primarily within the tumor microenvironment, particularly targeting CD8 + T cells. However, recent studies have highlighted a pivotal role of tumor-draining lymph nodes in mediating responses to immune checkpoint inhibitor therapy. This study aimed to elucidate the specific mechanisms by which tumor-draining lymph nodes respond to immune checkpoint inhibitor therapy and regulate the tumor microenvironment in human colorectal cancer. METHODS: We performed single-cell RNA sequencing and T cell receptor sequencing on tumor-draining lymph nodes and tumor tissues from patients with colorectal cancer. Through in-depth analysis of the single-cell data, we established the connection between TDLNs and tumor, and explored the impact of immune checkpoint inhibitor therapy on the immune microenvironment of tumor-draining lymph nodes. In addition, we conducted animal experiments to validate these findings. RESULTS: Our findings revealed that immune checkpoint inhibitor treatment induced the expansion of tumor-specific CD8 + effector memory T cells within tumor-draining lymph nodes, which may serve as a source for the progenitor-exhausted CD8 + T cells in the tumor microenvironment. Moreover, conventional dendritic cells type 1 and macrophages within tumor-draining lymph nodes facilitated this process. We also observed that immune checkpoint inhibitor therapy promoted the expansion of tumor-s...