Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study

作者：Jia-Xin Lei, Runxian Wang, Chuling Hu, Xiaoying Lou, Min‐Yi Lv, Chenghang Li, Baowen Gai, Xiaojian Wu, Ruoxu Dou, Du Cai, Feng Gao · 发表于：International Journal of Surgery · 年份：2024 · DOI：10.1097/js9.0000000000001684 · 被引用次数：16 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Immune cells in cancer

BACKGROUND: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. METHODS: The authors collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multiomics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. RESULTS: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. The authors subsequently employed a regularization alg...