Intratumoral tertiary lymphoid structure (TLS) maturation is influenced by draining lymph nodes of lung cancer

作者：Miao He, Qihua He, Xiuyu Cai, Jun Liu, Hongshen Deng, Feng Li, Ran Zhong, Yi Heng Lu, Haoxin Peng, Xiangrong Wu, Zisheng Chen, Shen Lao, Caichen Li, Jianfu Li, Jianxing He, Wenhua Liang · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2022-005539 · 被引用次数：85 · 研究领域：Cancer Immunotherapy and Biomarkers、Single-cell and spatial transcriptomics、IL-33, ST2, and ILC Pathways

BACKGROUND: Tertiary lymphoid structure (TLS) is an organized infiltration of immune cells, showing features of germinal center (GC) commonly seen in secondary lymphoid organs. However, its relationship with tumor-draining lymph nodes (TDLNs) has not been studied and we hypothesized that TDLN may influence maturation of intratumoral TLS in non-small cell lung cancer (NSCLC). METHODS: Tissue slides of 616 patients that had undergone surgeries were examined. Cox proportional hazard regression model was used to assess risk factors of patients' survival, and logistic regression model was used for their relationship with TLS. Single-cell RNA-sequencing (scRNA-seq) was employed to explore transcriptomic features of TDLNs. Immunohistochemistry, multiplex immunofluorescence and flow cytometry were performed to analyze cellular composition. Cellular components of NSCLC samples from The Cancer Genome Atlas database were inferred with Microenvironment Cell Populations-counter (MCP-counter) method. Murine NSCLC models were used to dissect underlying mechanisms for relationship between TDLN and TLS maturation. RESULTS: TLS was not. TDLN metastasis reduced the prognostic relevance of TLS, and was associated with less GC formation. Primary tumor sites showed reduced B cell infiltration in TDLN-positive patients, and scRNA-seq revealed diminished memory B cell formation in tumor-invaded TDLNs, together with an emphasis on weakened interferon (IFN)-γ response. Murine NSCLC models revealed tha...