Liu Chengsen, Cao Jiandong
Department of Radiotherapy, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China.
Department of Thoracic Surgery, Shenyang Chest Hospital and Tenth People's Hospital, Shenyang, Liaoning, China.
Front Oncol. 2025 May 22;15:1616904. doi: 10.3389/fonc.2025.1616904. eCollection 2025.
Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that form in non-lymphoid tissues in response to chronic inflammatory stimulation. Structurally and functionally resembling lymph nodes, TLS are primarily composed of B cells, T cells, dendritic cells, and other immune cell populations. Critically, TLS serve as direct sites for initiating anti-tumor immune responses. Within tumors, TLS facilitate the accumulation of immune cells-particularly effector subsets such as cytotoxic T cells and antibody-producing B cells-in the tumor microenvironment, thereby establishing a localized hub for both cellular and humoral immunity. This localized immune activation correlates with improved patient prognosis and enhanced responses to immunotherapy. In this review, we summarize the organization, formation drivers, detection markers, and the interplay between TLS and tumor-associated genes. Furthermore, we discuss the potential of TLS as biomarkers for immunotherapy efficacy and their translational clinical applications.
三级淋巴结构（TLS）是在慢性炎症刺激下于非淋巴组织中形成的异位淋巴结构。TLS在结构和功能上类似于淋巴结，主要由B细胞、T细胞、树突状细胞和其他免疫细胞群体组成。至关重要的是，TLS是启动抗肿瘤免疫反应的直接场所。在肿瘤内部，TLS促进免疫细胞——特别是效应子亚群，如细胞毒性T细胞和产生抗体的B细胞——在肿瘤微环境中的积累，从而建立一个细胞免疫和体液免疫的局部中心。这种局部免疫激活与患者预后改善和对免疫治疗的反应增强相关。在本综述中，我们总结了TLS的组织、形成驱动因素、检测标志物以及TLS与肿瘤相关基因之间的相互作用。此外，我们还讨论了TLS作为免疫治疗疗效生物标志物的潜力及其转化临床应用。
