a Department of Obstetrics, Gynecology & Reproductive Sciences , Yale University School of Medicine , New Haven , CT , USA.
b Department of Obstetrics and Gynecology , Bridgeport Hospital, Yale New Haven Health , Bridgeport , CT , USA.
Expert Opin Biol Ther. 2016 Aug;16(8):989-1004. doi: 10.1080/14712598.2016.1177018. Epub 2016 Apr 25.
The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune response against recurring cancer cells leading to long-term remissions for cancer patients. The use of immune checkpoint inhibitors, which work by targeting molecules that regulate immune responses, might be a promising avenue of immunotherapeutic research in gynecologic cancers.
This review focuses on the use of immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and the programmed death receptors such as PD-1 and PD1-ligand in gynecologic cancers. Combinatorial approaches utilizing immunotherapeutic agents with conventional treatments as well as immune-related response criteria and the adverse effects arising due to checkpoint inhibitor immunotherapy have been also discussed in the review.
After years of very little success, a better understanding of the pivotal role of the tumor microenvironment in suppressing anticancer immunity and the exploration of treatment regimens using immune checkpoint inhibitors alone or in combination have finally led to the development of effective cancer immunotherapies and to improve survival of patients with certain types of advanced cancers. While the clinical experience with immune checkpoint inhibitors in gynecologic cancer patients remains limited, early signal of clinical activity strongly suggest that immunotherapy will play a significant role in the year to come in at least a subset of gynecologic cancer patients.
免疫系统通过与癌细胞的动态关系在控制癌症方面发挥着关键作用。免疫疗法可以针对复发的癌细胞建立持续的免疫反应,从而使癌症患者获得长期缓解。免疫检查点抑制剂的使用,通过靶向调节免疫反应的分子,可能是妇科癌症免疫治疗研究的一个有前途的途径。
本综述重点介绍了针对细胞毒性 T 淋巴细胞抗原-4(CTLA-4)和程序性死亡受体(如 PD-1 和 PD-L1)的免疫检查点抑制剂在妇科癌症中的应用。该综述还讨论了免疫治疗药物与常规治疗相结合的联合方法,以及免疫相关反应标准和由于检查点抑制剂免疫治疗引起的不良反应。
经过多年的收效甚微,人们对肿瘤微环境在抑制抗癌免疫方面的关键作用有了更深入的了解,并探索了单独或联合使用免疫检查点抑制剂的治疗方案,最终开发出了有效的癌症免疫疗法,并提高了某些类型晚期癌症患者的生存率。虽然免疫检查点抑制剂在妇科癌症患者中的临床经验仍然有限,但早期的临床活性信号强烈表明,免疫疗法将在未来至少在一部分妇科癌症患者中发挥重要作用。