Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma

作者：Yang Liu, Shuangyan Ye, Shuai He, Dongmei Chi, Xiuzhi Wang, Yue‐Feng Wen, Dong Ma, Run‐Cong Nie, Xiang Pu, You Zhou, Zhao-Hui Ruan, Roujun Peng, Chun-Ling Luo, Panpan Wei, Guo‐Wang Lin, Jian Zheng, Qian Cui, Muyan Cai, Jing‐Ping Yun, Junchao Dong, Hai‐Qiang Mai, Xiaojun Xia, Jin‐Xin Bei · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-52153-4 · 被引用次数：96 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Single-cell and spatial transcriptomics

Abstract Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13 + cancer-associated fibroblasts, stem-like CXCL13 + CD8 + T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13 + cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13 + CD8 + T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.