Dolan Dawn E, Gupta Shilpa
Genitourinary Oncology Program, Moffitt Cancer Center, Tampa, FL 33612, USA.
Cancer Control. 2014 Jul;21(3):231-7. doi: 10.1177/107327481402100308.
Immunotherapeutic approaches to treating cancer have been evaluated during the last few decades with limited success. An understanding of the checkpoint signaling pathway involving the programmed death 1 (PD-1) receptor and its ligands (PD-L1/2) has clarified the role of these approaches in tumor-induced immune suppression and has been a critical advancement in immunotherapeutic drug development.
A comprehensive literature review was performed to identify the available data on checkpoint inhibitors, with a focus on anti-PD-1 and anti-PD-L1 agents being tested in oncology. The search included Medline, PubMed, the ClinicalTrials.gov registry, and abstracts from the American Society of Clinical Oncology meetings through April 2014. The effectiveness and safety of the available anti-PD-1 and anti-PD-L1 drugs are reviewed.
Tumors that express PD-L1 can often be aggressive and carry a poor prognosis. The anti-PD-1 and anti-PD-L1 agents have a good safety profile and have resulted in durable responses in a variety of cancers, including melanoma, kidney cancer, and lung cancer, even after stopping treatment. The scope of these agents is being evaluated in various other solid tumors and hematological malignancies, alone or in combination with other therapies, including other checkpoint inhibitors and targeted therapies, as well as cytotoxic chemotherapy.
The PD-1/PD-L1 pathway in cancer is implicated in tumors escaping immune destruction and is a promising therapeutic target. The development of anti-PD-1 and anti-PD-L1 agents marks a new era in the treatment of cancer with immunotherapies. Early clinical experience has shown encouraging activity of these agents in a variety of tumors, and further results are eagerly awaited from completed and ongoing studies.
在过去几十年中，对癌症的免疫治疗方法进行了评估，但成效有限。对涉及程序性死亡1（PD-1）受体及其配体（PD-L1/2）的检查点信号通路的理解，阐明了这些方法在肿瘤诱导的免疫抑制中的作用，并且是免疫治疗药物开发中的一项关键进展。
进行了全面的文献综述，以确定关于检查点抑制剂的现有数据，重点是正在肿瘤学中进行测试的抗PD-1和抗PD-L1药物。检索包括Medline、PubMed、ClinicalTrials.gov注册库以及截至2014年4月美国临床肿瘤学会会议的摘要。对现有抗PD-1和抗PD-L1药物的有效性和安全性进行了综述。
表达PD-L1的肿瘤通常具有侵袭性且预后较差。抗PD-1和抗PD-L1药物具有良好的安全性，并且在多种癌症中都产生了持久的反应，包括黑色素瘤、肾癌和肺癌，甚至在停止治疗后也是如此。正在单独或与其他疗法（包括其他检查点抑制剂和靶向疗法以及细胞毒性化疗）联合，在各种其他实体瘤和血液系统恶性肿瘤中评估这些药物的适用范围。
癌症中的PD-1/PD-L1通路与肿瘤逃避免疫破坏有关，是一个有前景的治疗靶点。抗PD-1和抗PD-L1药物的开发标志着癌症免疫治疗的新时代。早期临床经验已显示这些药物在多种肿瘤中具有令人鼓舞的活性，人们急切期待已完成和正在进行的研究能有进一步结果。
