Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia.
Int J Mol Sci. 2021 Mar 12;22(6):2907. doi: 10.3390/ijms22062907.
T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8 Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models.
T 细胞在肿瘤监测中发挥着关键作用，既能识别又能消除转化细胞。然而，随着肿瘤的建立，它们会形成自己的抑制性微环境，能够关闭 T 细胞的功能，从而使肿瘤得以持续生长。为了进一步了解肿瘤微环境，包括不同免疫细胞之间的相互作用及其在抗肿瘤免疫反应中的作用，已经进行了许多从小鼠模型到临床试验的研究。在这篇综述中，我们研究了肿瘤细胞用来降低其对 CD8 细胞毒性 T 淋巴细胞（CTL）可见性的机制，以及为克服这些肿瘤逃逸机制而尝试的治疗策略。接下来，我们总结了过去 10 年来增强嵌合抗原受体 T 细胞（CAR T 细胞）活性和持久性的最新进展，包括双特异性 CAR T 细胞设计和早期疗效证据。最后，我们研究了 T 细胞浸润和肿瘤消退的机制，并讨论了在小鼠肿瘤模型中研究 T 细胞功能的不同策略的优缺点。
