Tang Haidong, Qiu Xiangyan, Timmerman Casey, Fu Yang-Xin
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Methods Mol Biol. 2018;1845:275-286. doi: 10.1007/978-1-4939-8709-2_16.
Tumor microenvironments (TME) are usually immunosuppressive and prevent lymphocyte priming. Recent clinical trials have shown that cancer immunotherapy such as immune checkpoint inhibitors can induce unprecedented durable responses in patients with a variety of cancers. Tertiary lymphoid structures (TLS) can form inside or adjacent to tumor tissues due to persistent inflammation. The formation of TLS facilitates lymphocyte trafficking and infiltration into tumor tissues. It can also support effective antigen presentation and lymphocyte activation. Thus, TLS have become an intriguing target to manipulate antitumor immunity. Several therapeutics targeting TLS have been developed and shown promising antitumor effects in various mouse models. In this chapter, we describe the general approach to establish transplantable mouse tumor models for the study of immunotherapy. We introduce the strategies for therapy through systemic or local treatment targeting TLS. We also present approaches to evaluate the antitumor immune responses provoked by the therapies.
肿瘤微环境（TME）通常具有免疫抑制作用，并会阻止淋巴细胞启动。最近的临床试验表明，诸如免疫检查点抑制剂之类的癌症免疫疗法可在患有多种癌症的患者中诱导出前所未有的持久反应。由于持续性炎症，三级淋巴结构（TLS）可在肿瘤组织内部或附近形成。TLS的形成促进淋巴细胞向肿瘤组织的迁移和浸润。它还可以支持有效的抗原呈递和淋巴细胞激活。因此，TLS已成为操纵抗肿瘤免疫的一个引人关注的靶点。已经开发出几种靶向TLS的疗法，并在各种小鼠模型中显示出有前景的抗肿瘤作用。在本章中，我们描述了建立可移植小鼠肿瘤模型以用于免疫治疗研究的一般方法。我们介绍了通过全身或局部治疗靶向TLS的治疗策略。我们还展示了评估这些疗法引发的抗肿瘤免疫反应的方法。
