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

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作者：Liu Yang, Ye Shuang-Yan, He Shuai, Chi Dong-Mei, Wang Xiu-Zhi, Wen Yue-Feng, Ma Dong, Nie Run-Cong, Xiang Pu, Zhou You, Ruan Zhao-Hui, Peng Rou-Jun, Luo Chun-Ling, Wei Pan-Pan, Lin Guo-Wang, Zheng Jian, Cui Qian, Cai Mu-Yan, Yun Jing-Ping, Dong Junchao, Mai Hai-Qiang, Xia Xiaojun, Bei Jin-Xin
期刊：Nature Communications
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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.