Ghosh Chinmoy, Luong Gary, Sun Yue
Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
J Cancer. 2021 Mar 5;12(9):2735-2746. doi: 10.7150/jca.57334. eCollection 2021.
Cancer cells can evade the attack from host immune systems via hijacking the regulatory circuits mediated by immune checkpoints. Therefore, reactivating the antitumor immunity by blockade of immune checkpoints is considered as a promising strategy to treat cancer. Programmed death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) are critical immune checkpoint proteins that responsible for negative regulation of the stability and the integrity of T-cell immune function. Anti-PD-1/PD-L1 drugs have been developed for immune checkpoint blockade and can induce clinical responses across different types of cancers, which provides a new hope to cure cancer. However, the patients' response rates to current anti-PD-1 or anti-PD-L1 therapies are still low and many initial responders finally develop resistance to these therapies. In this review, we provides a snapshot of the PD-1/PD-L1 molecular structure, mechanisms controlling their expression, signaling modulated by PD-1/PD-L1, current anti-PD-1/PD-L1 therapies, and the future perspectives to overcome the resistance.
癌细胞可通过劫持免疫检查点介导的调节回路来逃避宿主免疫系统的攻击。因此，通过阻断免疫检查点来重新激活抗肿瘤免疫被认为是一种有前景的癌症治疗策略。程序性死亡蛋白1（PD-1）及其配体程序性死亡配体1（PD-L1）是关键的免疫检查点蛋白，负责对T细胞免疫功能的稳定性和完整性进行负调节。抗PD-1/PD-L1药物已被开发用于免疫检查点阻断，并可在不同类型的癌症中诱导临床反应，这为治愈癌症带来了新希望。然而，患者对当前抗PD-1或抗PD-L1疗法的反应率仍然较低，许多初始反应者最终会对这些疗法产生耐药性。在这篇综述中，我们概述了PD-1/PD-L1的分子结构、控制其表达的机制、由PD-1/PD-L1调节的信号传导、当前的抗PD-1/PD-L1疗法以及克服耐药性的未来前景。
