关键词: 生殖器肿瘤,女（雌）性, 免疫疗法, PD-1/PD-L1抑制剂, DNA错配修复, 微卫星不稳定性, 肿瘤突变高负荷

Abstract:

Recurrent or metastatic gynecologic tumors are usually resistant to conventional cancer therapies. Immunotherapy such as PD-1/PD-L1 blocking antibodies has revolutionized the treatment strategy, and even achieved unprecedentedly long durations of response in advanced malignancies including gynecologic tumors. Nevertheless, immunotherapy has met a bottleneck that the majority of patients do not have a good response to PD-1/PD-L1 blocking antibodies due to primary or acquired drug resistance, and the mechanisms are currently poorly understood. Currently, several hot issues are emphasized in clinical practice. First, the benefits of PD-1/PD-L1 blocking antibodies in the overall population are still very low. Therefore, it is a new trend that combination therapies with other agents are administrated to improve the antitumor efficacy. Second, the most widely investigated predictive biomarkers for immunotherapy are sufficiently validated for clinical use. There is an urgent need to identify biomarkers that upfront predict whether a patient is likely to respond to immunotherapy. Third, both hyperprogression and pseudo-hyperprogression pose challenges for immunotherapy, therefore it is important to assess how and when to evaluate the treatment efficacy. At the same time, how to evaluate and manage immune-related adverse events is an urgent focus of future research as well.

Key words: Genital neoplasms,Female, Immunotherapy, PD-1/PD-L1 blocking antibodies, DNA mismatch repair, Microsatellite instability, Tumor mutation burden-high