Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher maturity and/or higher density TLS are often associated with favorable clinical outcomes and immunotherapeutic response, mainly due to crosstalk between different proportions of immune cell subpopulations in TA-TLS. Therefore, TLS can be used as a marker to predict the efficacy of immunotherapy in immune checkpoint blockade (ICB). Developing efficient imaging and induction methods to study TA-TLS is crucial for enhancing anti-tumour immunity. The integration of imaging techniques with biological materials, including nanoprobes and hydrogels, alongside artificial intelligence (AI), enables non-invasive in vivo visualization of TLS. In this review, we explore the dynamic interactions among T and B cell subpopulations of varying phenotypes that contribute to the structural and functional diversity of TLS, examining both existing and emerging techniques for TLS imaging and induction, focusing on cancer immunotherapies and biomaterials. We also highlight novel therapeutic approaches of TLS that are being explored with the aim of increasing ICB treatment efficacy and predicting prognosis.

中文翻译：

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三级淋巴结构异质性决定肿瘤免疫力及临床应用前景

三级淋巴结构 (TLS) 是免疫细胞簇，其功能与二级淋巴器官 (SLO) 相似。虽然 TLS 通常与大多数癌症类型的抗肿瘤免疫反应相关，但它也被观察到充当促肿瘤免疫反应。 TLS 功能的异质性很大程度上取决于肿瘤浸润淋巴细胞 (TIL) 的组成和肿瘤相关 TLS (TA-TLS) 内细胞亚群的平衡。不同成熟度、密度和位置的 TA-TLS 可能对肿瘤免疫产生相反的影响。较高的成熟度和/或较高密度的 TLS 通常与良好的临床结果和免疫治疗反应相关，这主要是由于 TA-TLS 中不同比例的免疫细胞亚群之间的串扰。因此，TLS可以作为预测免疫检查点阻断（ICB）免疫疗法疗效的标志物。开发有效的成像和诱导方法来研究 TA-TLS 对于增强抗肿瘤免疫力至关重要。成像技术与生物材料（包括纳米探针和水凝胶）的集成以及人工智能（AI），可以实现 TLS 的非侵入性体内可视化。在这篇综述中，我们探讨了不同表型的 T 和 B 细胞亚群之间的动态相互作用，这些相互作用有助于 TLS 的结构和功能多样性，检查现有和新兴的 TLS 成像和诱导技术，重点关注癌症免疫疗法和生物材料。我们还重点介绍了正在探索的 TLS 新型治疗方法，其目的是提高 ICB 治疗效果和预测预后。