Zang Xingxing, Allison James P
Howard Hughes Medical Institute, Immunology Program, Ludwig Center of Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5271-9. doi: 10.1158/1078-0432.CCR-07-1030.
The activation and development of an adaptive immune response is initiated by the engagement of a T-cell antigen receptor by an antigenic peptide-MHC complex. The outcome of this engagement is determined by both positive and negative signals, costimulation and coinhibition, generated mainly by the interaction between the B7 family and their receptor CD28 family. The importance of costimulation and coinhibition of T cells in controlling immune responses is exploited by tumors as immune evasion pathways. Absence of the expression of costimulatory B7 molecules renders tumors invisible to the immune system, whereas enhanced expression of inhibitory B7 molecules protects them from effective T cell destruction. Therefore, the manipulation of these pathways is crucial for developing effective tumor immunotherapy. Translation of our basic knowledge of costimulation and coinhibition into early clinical trials has shown considerable promise.
适应性免疫反应的激活和发展是由抗原肽-MHC复合物与T细胞抗原受体的结合引发的。这种结合的结果由主要由B7家族与其受体CD28家族之间的相互作用产生的正信号和负信号、共刺激和共抑制决定。肿瘤利用T细胞的共刺激和共抑制在控制免疫反应中的重要性作为免疫逃逸途径。共刺激B7分子表达缺失使肿瘤对免疫系统不可见，而抑制性B7分子的增强表达保护它们免受有效的T细胞破坏。因此，操纵这些途径对于开发有效的肿瘤免疫疗法至关重要。将我们关于共刺激和共抑制的基础知识转化为早期临床试验已显示出相当大的前景。
