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