文章：

抗癌免疫中的三级淋巴结构

Tertiary lymphoid structures in anticancer immunity

原文发布日期：2024-08-08

DOI: 10.1038/s41568-024-00728-0

类型: Review Article

开放获取: 否

英文摘要：

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment. TLS have also garnered considerable interest as a predictive biomarker of the response to antitumour therapies, including immune checkpoint blockade and, possibly, chemotherapy. However, several important questions still remain regarding the definition of TLS in terms of both their cellular composition and functions. Here, we summarize the current views on the composition of TLS at different stages of their development. We also discuss the role of B cells and T cells associated with TLS and their dialogue in mounting antibody and cellular antitumour responses, as well as some of the various mechanisms that negatively regulate antitumour activity of TLS. The prognostic value of TLS to the clinical outcome of patients with cancer and the relationship between TLS and the response to therapy are then addressed. Finally, we present some preclinical evidence that favours the idea that manipulating the formation and function of TLS could lead to a potent next-generation cancer immunotherapy.

摘要翻译： 

三级淋巴结构（TLS）是短暂的异位淋巴聚集体，可在其中形成适应性抗肿瘤细胞及体液免疫应答。最初在非小细胞肺癌中被描述为与良好临床结局相关的功能性免疫淋巴结构，随后发现TLS也存在于多种其他癌种、黑色素瘤和肉瘤中，并与免疫治疗反应增强相关。鉴于TLS可能提升接受免疫检查点抑制剂治疗的癌症患者生存率，将其作为治疗策略的临床应用正日趋成熟。TLS作为预测抗肿瘤治疗（包括免疫检查点阻断及可能化疗）反应的生物标志物也引起广泛关注。然而，关于TLS在细胞组成和功能方面的定义仍存在重要问题。本文总结了当前对不同发育阶段TLS组成结构的认识，探讨了TLS相关B细胞与T细胞的作用及其在介导抗体与细胞抗肿瘤反应中的协同机制，并阐述了负向调控TLS抗肿瘤活性的多种机理。同时分析了TLS对癌症患者临床结局的预后价值，以及TLS与治疗反应之间的关系。最后，我们提供了临床前证据支持这一观点：调控TLS的形成和功能有望催生新一代高效癌症免疫疗法。

原文链接：

Tertiary lymphoid structures in anticancer immunity