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

Tertiary lymphoid structures (TLS) are immune cell aggregates linked with cancer outcomes, but their interactions with tumor cell aggregates are unclear. This study uses nasopharyngeal carcinoma (NPC) as a model, analyzing single-cell transcriptomes of 343,829 cells from 77 samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumors. Key TLS cell populations were identified, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Germinal center reaction matures plasma cells, which intersperse with tumor cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. TLS-related cell signatures correlate with prognosis and PD-1 blockade response.

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