Department of Immunology & Center for Inflammation & Cancer, MD Anderson Cancer Center, Houston, TX 77030, USA.
Immunotherapy. 2013 May;5(5):513-531. doi: 10.2217/imt.13.33.
T cells are the master regulators of adaptive immune responses and maintenance of their tolerance is critical to prevent autoimmunity. However, in the case of carcinogenesis, the tumor microenvironment aids T-cell tolerance, which contributes to uncontrolled tumor growth. Recently, there has been significant progress in understanding the intrinsic extracellular (positive and negative costimulatory molecules on APCs) and intracellular mechanisms (E3 ubiquitin ligases, transcriptional and epigenetic repressors), as well as extrinsic mechanisms (Tregs and tolerogenic dendritic cells) that are required for the implementation and maintenance of T-cell tolerance. Ultimately, understanding and manipulating T-cell tolerance will help to break the tolerance state in cancer.
T 细胞是适应性免疫反应的主要调节者,维持其耐受对于防止自身免疫至关重要。然而,在致癌的情况下,肿瘤微环境有助于 T 细胞耐受,这导致肿瘤不受控制的生长。最近,人们在理解内在的细胞外(APC 上的正性和负性共刺激分子)和细胞内机制(E3 泛素连接酶、转录和表观遗传抑制剂)以及外在机制(Tregs 和耐受树突状细胞)方面取得了重大进展,这些机制对于 T 细胞耐受的实施和维持是必需的。最终,理解和操纵 T 细胞耐受将有助于打破癌症中的耐受状态。