Welters Marij J P, Piersma Sytse J, van der Burg Sjoerd H
Department of Immunohematology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Expert Opin Biol Ther. 2008 Sep;8(9):1365-79. doi: 10.1517/14712598.8.9.1365.
Immunotherapy against cancer does not result in impressive clinical responses. Failure of vaccine-induced T-cell-mediated immunotherapy to improve therapeutic results occurs for many reasons, including regulatory networks imposed by growing tumours, intrinsic properties of cancer cells, suboptimal design of therapeutic vaccines and subversion of the immune system. Most vaccines are incapable of inducing strong immunity, the vaccine's capacity to induce effector T cells is blocked by regulatory T cells (Tregs) in the lymph nodes, the vaccine-induced T cells are not able to infiltrate the tumour, tumour-infiltrating T cells cannot exert their effector function due to locally present Tregs and/or vaccines may induce/boost Tregs.
OBJECTIVE/METHODS: We focus on the negative effects of Tregs in cancer immunotherapy and highlight potential therapeutic options to counteract these.
Interplay and balance between Tregs and effector cells determines the efficacy of vaccines and thereby clinical outcome.
癌症免疫疗法并未带来令人瞩目的临床反应。疫苗诱导的T细胞介导的免疫疗法未能改善治疗效果,原因众多,包括不断生长的肿瘤施加的调节网络、癌细胞的内在特性、治疗性疫苗设计欠佳以及免疫系统的颠覆。大多数疫苗无法诱导强大的免疫力,疫苗诱导效应T细胞的能力在淋巴结中被调节性T细胞(Tregs)阻断,疫苗诱导的T细胞无法浸润肿瘤,肿瘤浸润性T细胞由于局部存在的Tregs而无法发挥其效应功能,和/或疫苗可能诱导/增强Tregs。
目的/方法:我们关注Tregs在癌症免疫疗法中的负面影响,并强调对抗这些影响的潜在治疗选择。
Tregs与效应细胞之间的相互作用和平衡决定了疫苗的疗效,进而决定了临床结果。