Heong Valerie, Ngoi Natalie, Tan David Shao Peng
Department of Hematology-Oncology, National University Hospital, Singapore, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
J Gynecol Oncol. 2017 Mar;28(2):e20. doi: 10.3802/jgo.2017.28.e20. Epub 2016 Dec 14.
In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers.
近年来,我们对免疫细胞和肿瘤微环境(TME)中免疫调节信号通路的理解取得了进展,这使得人们对癌症免疫疗法重新产生了兴趣。特别是,靶向免疫检查点受体如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)的免疫疗法已在包括妇科癌症在内的多种肿瘤中显示出临床活性。本综述将聚焦于免疫检查点抑制剂治疗作用的新兴临床数据,以及在妇科癌症背景下提高这类化合物疗效的潜在策略。预计未来基于生物标志物的临床试验将进一步深入了解免疫疗法反应和耐药的潜在机制,并有助于指导我们设计有可能增强免疫疗法对妇科癌症患者益处的联合治疗方案。