Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, 610 University Ave, 700U, 7-305W, Toronto, ON, M5G 2M9, Canada.
University of New South Wales, Kensington, NSW, Australia.
Breast Cancer Res Treat. 2022 Jan;191(2):257-267. doi: 10.1007/s10549-021-06431-0. Epub 2021 Nov 3.
The breast cancer tumour microenvironment (BC-TME) is characterized by significant cellular and spatial heterogeneity that has important clinical implications and can affect response to therapy. There is a growing need to develop methods that reliably quantify and characterize the BC-TME and model its composition and functions in experimental systems, in the hope of developing new treatments for patients. In this review, we examine the role of immune-activating cells (including tumour-infiltrating lymphocytes and natural killer cells) and immune inhibitory cells (including T regulatory cells, tumour-associated macrophages and myeloid-derived suppressor cells) in the BC-TME. We summarize methods being used to characterize the microenvironment, with specific attention to pre-clinical models including co-cultures, organoids, and genetically modified and humanized mouse models. Finally, we explore the implications and applications of existing preclinical data for drug development and highlight several drugs designed to alter the BC-TME in order to improve treatment outcomes for patients.
乳腺癌肿瘤微环境(BC-TME)的特点是显著的细胞和空间异质性,这具有重要的临床意义,并可能影响治疗反应。因此,人们越来越需要开发可靠的方法来定量和描述 BC-TME,并在实验系统中模拟其组成和功能,以期为患者开发新的治疗方法。在这篇综述中,我们研究了免疫激活细胞(包括肿瘤浸润淋巴细胞和自然杀伤细胞)和免疫抑制细胞(包括 T 调节细胞、肿瘤相关巨噬细胞和髓系来源的抑制细胞)在 BC-TME 中的作用。我们总结了用于描述微环境的方法,特别关注包括共培养物、类器官和基因修饰及人源化小鼠模型在内的临床前模型。最后,我们探讨了现有临床前数据在药物开发方面的意义和应用,并强调了几种旨在改变 BC-TME 以改善患者治疗效果的药物。