美国匹兹堡大学医学院Dario A. A. Vignali研究组撰写综述文章，阐述了PD-1、PD-L1和CTLA-4以外的抑制受体和配体。2019年10月14日的《自然—免疫学》在线发表了这篇综述文章。

文章说，尽管针对抑制受体（IRs）CTLA-4、PD-1或PD-L1的免疫疗法已在癌症方面取得了实质性的临床进展，但仍有相当一部分患者对治疗没有效果。

靶向新型IR-配体途径结合当前的免疫疗法可改善临床疗效。新的临床免疫疗法靶向T细胞表达的IR（LAG-3，TIM-3和TIGIT）以及B7家族中的抑制性配体（B7-H3，B7-H4和B7-H5），尽管其中许多靶标具有复杂的生物学和不清楚的作用机制。在靶向这些IR方面仅取得了很少的临床效果，当前的免疫治疗设计可能不是最佳的。

这篇综述涵盖了靶向新型IR-配体途径的生物学及其免疫疗法的当前临床状况，无论是单一疗法还是与PD-1或其配体PD-L1的抗体联用。对这些靶标的基础生物学的进一步了解对于开发有效的癌症免疫疗法至关重要。

附：英文原文

Title: Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups

Author: Lawrence P. Andrews, Hiroshi Yano, Dario A. A. Vignali

Issue&Volume: 2019-10-14

Abstract: 

Although immunotherapeutics targeting the inhibitory receptors (IRs) CTLA-4, PD-1 or PD-L1 have made substantial clinical progress in cancer, a considerable proportion of patients remain unresponsive to treatment. Targeting novel IR–ligand pathways in combination with current immunotherapies may improve clinical outcomes. New clinical immunotherapeutics target T cell–expressed IRs (LAG-3, TIM-3 and TIGIT) as well as inhibitory ligands in the B7 family (B7-H3, B7-H4 and B7-H5), although many of these targets have complex biologies and unclear mechanisms of action. With only modest clinical success in targeting these IRs, current immunotherapeutic design may not be optimal. This Review covers the biology of targeting novel IR–ligand pathways and the current clinical status of their immunotherapeutics, either as monotherapy or in combination with antibody to PD-1 or to its ligand PD-L1. Further understanding of the basic biology of these targets is imperative to the development of effective cancer immunotherapies.

DOI: 10.1038/s41590-019-0512-0

Source: https://www.nature.com/articles/s41590-019-0512-0