妇科恶性肿瘤免疫治疗进展

Progress in Immunotherapy of Gynecological Malignant Tumors

传统治疗对晚期/复发妇科肿瘤的效果较差,以程序性死亡受体1及其配体(PD-1/PD-L1)抑制剂为主的免疫治疗为这些患者提供了新的治疗选择,甚至为一些原来没有治疗希望的患者带来了治愈的可能,因此成为近年研究的热点。但是,PD-1/PD-L1抑制剂对大多数晚期/复发妇科肿瘤患者无效(原发耐药),或者疗效持续时间短(继发耐药),成为免疫治疗的瓶颈。目前,临床上关注的问题主要有以下几个:①PD-1/PD-L1抑制剂单药的总体治疗效果欠佳,为了提高治疗效果,与其他药物联合应用成为新趋势;②目前临床常用的预测药物疗效的分子标志物的预测价值有限,因此,找到更为有效的分子标志物,将对免疫治疗可能有效的患者分流出来,具有重要的临床意义;③应用PD-1/PD-L1抑制剂后可能存在超进展、假性超进展等问题,因此对免疫治疗的疗效进行及时准确的评估也非常重要。此外,PD-1/PD-L1抑制剂相关不良事件的评估以及治疗等问题也备受关注。

Recurrent ormetastatic 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.