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.

三级淋巴结构（TLS）是短暂的异位淋巴聚集体，可以在其中产生适应性抗肿瘤细胞和体液反应。 TLS 最初在非小细胞肺癌中被描述为功能性免疫淋巴结构，与更好的临床结果相关，现在也在许多其他癌症以及黑色素瘤和肉瘤中发现了 TLS，并且与免疫治疗反应的改善相关。由于 TLS 在提高接受免疫检查点抑制剂治疗的癌症患者的生存率方面可能发挥作用，因此 TLS 作为一种治疗策略的应用现已成熟。 TLS 作为抗肿瘤治疗（包括免疫检查点阻断和可能的化疗）反应的预测生物标志物也引起了相当大的兴趣。然而，关于 TLS 的细胞组成和功能定义，仍然存在一些重要问题。在这里，我们总结了当前对于 TLS 在不同发展阶段的构成的看法。我们还讨论了与 TLS 相关的 B 细胞和 T 细胞的作用及其在产生抗体和细胞抗肿瘤反应中的对话，以及负调节 TLS 抗肿瘤活性的一些机制。然后讨论 TLS 对癌症患者临床结果的预后价值以及 TLS 与治疗反应之间的关系。最后，我们提出了一些临床前证据，支持这样的观点：操纵 TLS 的形成和功能可能会带来有效的下一代癌症免疫疗法。