免疫治疗在晚期或复发性子宫内膜癌中的应用进展

Advances in immunotherapy in advanced or recurrent endometrial carcinoma

子宫内膜癌(EC)是常见的妇科恶性肿瘤之一,由于肥胖和人口老龄化的加剧,其发病率逐渐上升。尽管早期EC通过手术治疗预后一般良好,但仍有部分患者出现或发展为转移性或复发性疾病。近年来,免疫治疗取得了新的进展,在晚期或复发性子宫内膜癌的治疗中具有重要地位,目前其免疫治疗主要包括免疫检查点抑制剂,如程序性细胞死亡蛋白1/程序性细胞死亡配体1抑制剂,细胞毒性T淋巴细胞相关蛋白4抑制剂,其他免疫治疗还包括嵌合抗原受体T细胞免疫疗法,肿瘤疫苗等,联合聚二磷酸腺苷核糖聚合酶抑制剂或靶向药物是研究热点,可以提高客观缓解率,产生附加效应甚至协同效应。免疫检查点抑制剂治疗微卫星不稳定和错配修复缺陷型子宫内膜癌疗效较好,在其他类型肿瘤中仍有待试验。细胞毒性T淋巴细胞相关蛋白4与免疫抑制检查点联合治疗有其独特优势,但是安全性和有效性还需要大量试验验证。联合聚二磷酸腺苷核糖聚合酶(PARP)抑制剂或靶向药物,药物种类和剂量,需要深入挖掘,以在最小副作用的前提下获得最佳疗效。对于癌症疫苗,有研究证实疫苗可以预防EC复发,但其安全性、有效性仍需大量临床试验进行验证。在未来免疫相关生物标志物的研究也将有助于预测EC治疗预后,对免疫治疗的研究具有重要意义。

Endometrial cancer(EC)is one of the most common gynecological malignancies,and its incidence is increasing with the increase of obesity and aging population.Although the prognosis of early EC with surgical treatment is generally good,some patients still develop or develop metastatic or recurrent disease.In recent years,immunotherapy has made new progress and plays an important role in the treatment of advanced or recurrent EC.Immunotherapy mainly includes immune checkpoint inhibitors,such as programmed cell death 1/programmed cell death ligand-1(PD-1/PD-L1)inhibitors,cytotoxic T-lymphocyte-associated protein 4(CTLA-4)inhibitors.Other immunotherapies include chimeric antigen receptor T cell(CAR-T)cell immunotherapy,tumor vaccine,etc.Combined with poly-ADP-ribose polymerase(PARP)inhibitors or targeted drugs is a hotspot,which can improve the objective response rate and produce additional effects or even synergistic effects.Immuno-checkpoint inhibitors are effective in the treatment of microsatellite unstable and mismatch repair defect endometrial carcinoma,but still need to be tested in other tumor types.The combination therapy of CTLA-4 and immunosuppressive checkpoint has its unique advantages,but its safety and efficacy need to be verified in a large number of trials.Combined with PARP inhibitors or targeted drugs,drug types and dosages need to be explored in order to achieve optimal efficacy with minimal side effects.As for cancer vaccine,studies have confirmed that the vaccine can prevent EC recurrence,but its safety and effectiveness still need to be verified.In the future,the study of immune-related biomarkers will also help to predict the prognosis of EC treatment,which is of great significance for the study of immunotherapy.