Anderson Ana C, Joller Nicole, Kuchroo Vijay K
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
Immunity. 2016 May 17;44(5):989-1004. doi: 10.1016/j.immuni.2016.05.001.
Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors, although they belong to the same class of receptors as PD-1 and CTLA-4, exhibit unique functions, especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic.
共抑制受体，如细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性死亡受体1（PD-1），在调节T细胞反应中发挥重要作用，并且已被证明是慢性疾病背景下的有效靶点，在这些疾病中，T细胞上组成性共抑制受体的表达会抑制效应T细胞反应。不幸的是，许多患者仍然对靶向CTLA-4和PD-1的疗法没有反应。正在临床试验中探索的下一波共抑制受体靶点包括淋巴细胞激活基因3（Lag-3）、T细胞免疫球蛋白黏蛋白3（Tim-3）和T细胞免疫受体Ig和ITIM结构域（TIGIT）。这些受体虽然与PD-1和CTLA-4属于同一类受体，但具有独特的功能，尤其是在调节免疫不同方面的组织部位。对这些受体特殊功能的进一步了解将为这些靶向受体的疗法在临床上的合理应用提供依据。
