Yanaihara Nozomu, Tse Ka Yu, Lee Sung Jong, Yoo Ji Geun, Wilailak Sarikapan
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong.
Int J Gynaecol Obstet. 2025 Sep;171 Suppl 1:166-188. doi: 10.1002/ijgo.70280.
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by leveraging the immune system's capacity to fight gynecologic cancer. This review summarizes the current status and future perspectives of ICIs in the treatment of cervical, endometrial, and ovarian cancers and rare tumors. ICIs have demonstrated significant efficacy in tumors with high tumor mutational burden and immune markers such as PD-L1 expression and microsatellite instability. In cervical cancer, the integration of ICIs has shown promise at various stages of treatment, including advanced and recurrent settings. In endometrial cancer, molecular classification has facilitated targeted immunotherapy strategies, with notable success in mismatch repair-deficient (dMMR) tumors. However, challenges remain in the treatment of microsatellite stable endometrial and epithelial ovarian cancers due to their relatively low immunogenicity. Combination therapies, including ICIs with angiogenesis inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, or chemotherapy, are being actively investigated to improve response rates. Several phase II and case series showed promising response to ICIs in vulvar/vaginal cancer and gestational trophoblastic neoplasia, though the efficacy in genital tract melanoma is still unclear. Despite these advances, the management of immune-related adverse events and the identification of reliable biomarkers for patient selection remain critical. ICIs are poised to redefine the therapeutic landscape of gynecologic oncology, offering hope for improved outcomes and personalized treatment strategies.
免疫检查点抑制剂(ICIs)通过利用免疫系统对抗妇科癌症的能力,彻底改变了癌症治疗方式。本综述总结了ICIs在宫颈癌、子宫内膜癌、卵巢癌及罕见肿瘤治疗中的现状和未来前景。ICIs在具有高肿瘤突变负荷和免疫标志物(如PD-L1表达和微卫星不稳定性)的肿瘤中已显示出显著疗效。在宫颈癌中,ICIs的整合在包括晚期和复发期在内的各个治疗阶段都显示出了前景。在子宫内膜癌中,分子分类促进了靶向免疫治疗策略的发展,在错配修复缺陷(dMMR)肿瘤中取得了显著成功。然而,由于微卫星稳定的子宫内膜癌和上皮性卵巢癌免疫原性相对较低,其治疗仍面临挑战。包括ICIs与血管生成抑制剂、聚(ADP-核糖)聚合酶(PARP)抑制剂或化疗联合的疗法正在积极研究中,以提高缓解率。几个II期试验和病例系列显示,ICIs对外阴/阴道癌和妊娠滋养细胞肿瘤有良好反应,尽管其对生殖道黑色素瘤的疗效仍不明确。尽管取得了这些进展,但免疫相关不良事件的管理以及识别可靠的生物标志物用于患者选择仍然至关重要。ICIs有望重新定义妇科肿瘤学的治疗格局,为改善治疗效果和个性化治疗策略带来希望。