肿瘤治疗中的 PD-1 通路抑制剂。
Inhibitors of the PD-1 Pathway in Tumor Therapy.
机构信息
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115.
出版信息
J Immunol. 2018 Jan 15;200(2):375-383. doi: 10.4049/jimmunol.1701044.
The programmed death 1 (PD-1) pathway delivers inhibitory signals that function as a brake for immune responses. This pathway limits the initiation and duration of immune responses, thereby protecting tissues from immune-mediated damage and autoimmune diseases. However, the PD-1 pathway also inhibits immune responses to tumors. The critical role of PD-1 in preventing antitumor immunity is demonstrated by the transformative effects of PD-1 pathway blockade in a broad range of cancers with the hallmark of durability of response. Despite this success, most patients do not respond to PD-1 monotherapy, and some patients experience adverse events. In this review, we discuss the functions of the PD-1 pathway and its translation to cancer immunotherapy. We also consider current challenges and opportunities for PD-1 cancer immunotherapy, including mechanisms of response and resistance, identification of biomarkers of response to PD-1 therapy, characterization and treatment of PD-1 therapy-related adverse events, and development of safe and effective combination therapies.
程序性死亡 1（PD-1）途径传递抑制信号，作为免疫反应的制动器。该途径限制了免疫反应的启动和持续时间，从而保护组织免受免疫介导的损伤和自身免疫性疾病的影响。然而，PD-1 途径也抑制了对肿瘤的免疫反应。PD-1 途径阻断在广泛的癌症中具有标志性的持久性反应，证明了 PD-1 在预防抗肿瘤免疫中的关键作用。尽管取得了这一成功，但大多数患者对 PD-1 单药治疗没有反应，有些患者出现了不良反应。在这篇综述中，我们讨论了 PD-1 途径的功能及其在癌症免疫治疗中的转化。我们还考虑了 PD-1 癌症免疫治疗的当前挑战和机遇，包括反应和耐药机制、PD-1 治疗反应生物标志物的鉴定、PD-1 治疗相关不良反应的特征和治疗以及安全有效的联合治疗的开发。
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