聚腺苷二磷酸核糖聚合酶抑制剂与卵巢癌免疫治疗调控的研究现状

doi:10.3877/cma.j.issn.1673-5250.2026.01.003

中华妇幼临床医学杂志(电子版) ›› 2026, Vol. 22 ›› Issue (01) : 13 -18. doi: 10.3877/cma.j.issn.1673-5250.2026.01.003

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聚腺苷二磷酸核糖聚合酶抑制剂与卵巢癌免疫治疗调控的研究现状

杨光淏, 刘臻妍, 杨宏英^†(

)

昆明医科大学第三附属医院妇科，昆明　650000

收稿日期:2026-01-02 修回日期:2026-01-15 出版日期:2026-02-01
通信作者: 杨宏英

Current research status on poly ADP-ribose polymerase inhibitors and regulation of immunotherapy for patients with ovarian cancer

Guanghao Yang, Zhenyan Liu, Hongying Yang^†()

Department of Gynecology, Third Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China

Received:2026-01-02 Revised:2026-01-15 Published:2026-02-01
Corresponding author: Hongying Yang
Supported by:
Basic Research Program in Yunnan Province (Joint Project of Yunnan Province Science and Technology Department and Kunming Medical University)(202201AY070001-138, 202201AY070001-162); Yunnan Province " Ten Thousand People Plan"(YNWR-MY-2019-039); Innovative Research Team of Yunnan Province(202305AS350020); Scientific Research Project of the Clinical Medical Center of Yunnan Province(20241223231121)

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杨光淏, 刘臻妍, 杨宏英. 聚腺苷二磷酸核糖聚合酶抑制剂与卵巢癌免疫治疗调控的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2026, 22(01): 13-18.

Guanghao Yang, Zhenyan Liu, Hongying Yang. Current research status on poly ADP-ribose polymerase inhibitors and regulation of immunotherapy for patients with ovarian cancer[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2026, 22(01): 13-18.

卵巢癌是导致患者病死率最高的妇科恶性肿瘤，临床诊断时晚期患者占比高达70%，传统手术联合铂类化疗后患者复发率高。卵巢癌患者的肿瘤免疫微环境呈现典型的"冷"肿瘤特征，导致免疫检查点抑制剂(ICI)单药治疗对其客观缓解率(ORR)普遍≤10%。近年研究发现，聚腺苷二磷酸-核糖聚合酶(PARP)抑制剂除通过"合成致死"机制靶向癌细胞DNA修复缺陷外，还具有重塑肿瘤免疫微环境的关键作用。临床研究结果显示，PARP抑制剂联合ICI治疗可提升卵巢癌患者的ORR，但是其联合策略迄今尚存在挑战性。笔者拟就卵巢癌的肿瘤免疫微环境、PARP抑制剂对卵巢癌患者的治疗及参与卵巢癌免疫治疗调控作用的最新研究现状进行阐述，旨在为开发PARP抑制剂维持治疗时代的卵巢癌患者免疫治疗方案提供一定思路。

关键词: 肿瘤微环境, 免疫抑制剂, 多(ADP核糖)聚合酶抑制剂, 免疫疗法, 免疫检查点抑制剂, 女(雌)性

Ovarian cancer ranks as the gynecological malignancy with the highest mortality rate, with approximately 70% of patients presenting at an advanced stage upon clinical diagnosis. Despite conventional treatment involving surgery plus platinum-based chemotherapy, the recurrence rate remains high. The tumor immune microenvironment of ovarian cancer exhibits typical " cold tumor" features, contributing to a suboptimal objective response rate (ORR) of ≤10% with immune checkpoint inhibitor (ICI) monotherapy. In recent years, studies have demonstrated that poly ADP-ribose polymerase (PARP) inhibitors not only target DNA repair defects in cancer cells via the " synthetic lethality" pathway, but also exert a pivotal role in remodeling the tumor immune microenvironment. Clinical evidence indicates that combination therapy with PARP inhibitors and ICI enhances the ORR in ovarian cancer patients; yet, optimizing this combination regimen remains challenging to date. This review summarizes the latest advances in the ovarian cancer tumor immune microenvironment, the therapeutic efficacy and regulatory effects of PARP inhibitors in ovarian cancer immunotherapy, with the goal of providing insights for developing immunotherapy strategies for ovarian cancer patients in the era of PARP inhibitors maintenance therapy.

Key words: Tumor microenvironment, Immunosuppressive agents, Poly(ADP-ribose) polymerase inhibitors, Immunotherapy, Immune checkpoint inhibitor, Female

表1 ICI单药治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	免疫药物	患者特征	样本量(例)	主要终点	结果
KEYNOTE-100^[25]	帕博利珠单抗(pembrolizumab)	复发性卵巢癌(铂耐药/铂敏感)	376	ORR	总体ORR为8%，在PD-L1高表达亚组(CPS≥10分)中，则ORR更高
JAVELIN Ovarian 100^[26]	阿维鲁单抗(avelumab)vs化疗(卡铂＋紫杉醇)	初治上皮性卵巢癌	998	PFS期	阿维鲁单抗维持治疗组PFS期为11.6个月，化疗对照组为11.5个月
NINJA^[27]	纳武利尤单抗(nivolumab)vs化疗(吉西他滨/聚乙二醇化脂质体阿霉素)	复发性铂耐药卵巢癌	316	OS期	①OS期：nivolumab组为10.12个月，化疗组为12.09个月(HR＝1.03，P＝0.808)。②PFS期(次要终点)：nivolumab组为2.04个月，化疗组为3.84个月(HR＝1.46，P＝0.002)

表1 ICI单药治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	免疫药物	患者特征	样本量(例)	主要终点	结果
KEYNOTE-100^[25]	帕博利珠单抗(pembrolizumab)	复发性卵巢癌(铂耐药/铂敏感)	376	ORR	总体ORR为8%，在PD-L1高表达亚组(CPS≥10分)中，则ORR更高
JAVELIN Ovarian 100^[26]	阿维鲁单抗(avelumab)vs化疗(卡铂＋紫杉醇)	初治上皮性卵巢癌	998	PFS期	阿维鲁单抗维持治疗组PFS期为11.6个月，化疗对照组为11.5个月
NINJA^[27]	纳武利尤单抗(nivolumab)vs化疗(吉西他滨/聚乙二醇化脂质体阿霉素)	复发性铂耐药卵巢癌	316	OS期	①OS期：nivolumab组为10.12个月，化疗组为12.09个月(HR＝1.03，P＝0.808)。②PFS期(次要终点)：nivolumab组为2.04个月，化疗组为3.84个月(HR＝1.46，P＝0.002)

表2 PARP抑制剂联合ICI治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	分组	结果
TOPACIO/KEYNOTE-162^[34]	复发卵巢癌(不限BRCA状态)组(n＝55)，采取尼拉帕利＋帕博利珠单抗治疗	ORR为18%(3例为CR，8例为PR)，DCR为65%
DUO-O^[32]	研究对象均为非BRCA突变HRD呈阳性和非BRCA突变ITT卵巢癌患者。化疗阶段：组1(n＝143)采取卡铂/紫杉醇＋贝伐珠单抗治疗措施；组2(n＝148)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施；组3(n＝140)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施。维持治疗阶段：组1采取贝伐珠单抗单独治疗＋安慰剂治疗措施；组2采取贝伐珠单抗＋度伐利尤单抗治疗＋安慰剂治疗措施；组3采取贝伐珠单抗＋度伐利尤单抗＋奥拉帕利治疗措施	非BRCA突变HRD呈阳性患者中的mPFS期：组1、2、3分别为23.0、24.4、37.3个月。非BRCA突变ITT患者中的mPFS期：组1、2、3分别为19.3、20.6、24.2个月，组1 vs组3(HR＝0.63，95%CI：0.52~0.76，P<0.000 1)
ENGOT-OV41/GEICO 69-O/ANITA^[33]	研究对象：417例患者，其中15%为BRCA突变者(n＝63)，36%为PD-L1呈阳性者(n＝150)，66%为TFIP>12个月者(n＝275)。联合组(n＝209)：采取阿替利珠单抗＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施；标准组(n＝208)：采取安慰剂＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施	PFS期：联合组、标准组分别为11.2、10.1个月(HR＝0.89，95%CI：0.71~1.10，P＝0.28)

表2 PARP抑制剂联合ICI治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	分组	结果
TOPACIO/KEYNOTE-162^[34]	复发卵巢癌(不限BRCA状态)组(n＝55)，采取尼拉帕利＋帕博利珠单抗治疗	ORR为18%(3例为CR，8例为PR)，DCR为65%
DUO-O^[32]	研究对象均为非BRCA突变HRD呈阳性和非BRCA突变ITT卵巢癌患者。化疗阶段：组1(n＝143)采取卡铂/紫杉醇＋贝伐珠单抗治疗措施；组2(n＝148)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施；组3(n＝140)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施。维持治疗阶段：组1采取贝伐珠单抗单独治疗＋安慰剂治疗措施；组2采取贝伐珠单抗＋度伐利尤单抗治疗＋安慰剂治疗措施；组3采取贝伐珠单抗＋度伐利尤单抗＋奥拉帕利治疗措施	非BRCA突变HRD呈阳性患者中的mPFS期：组1、2、3分别为23.0、24.4、37.3个月。非BRCA突变ITT患者中的mPFS期：组1、2、3分别为19.3、20.6、24.2个月，组1 vs组3(HR＝0.63，95%CI：0.52~0.76，P<0.000 1)
ENGOT-OV41/GEICO 69-O/ANITA^[33]	研究对象：417例患者，其中15%为BRCA突变者(n＝63)，36%为PD-L1呈阳性者(n＝150)，66%为TFIP>12个月者(n＝275)。联合组(n＝209)：采取阿替利珠单抗＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施；标准组(n＝208)：采取安慰剂＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施	PFS期：联合组、标准组分别为11.2、10.1个月(HR＝0.89，95%CI：0.71~1.10，P＝0.28)

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Current research status on poly ADP-ribose polymerase inhibitors and regulation of immunotherapy for patients with ovarian cancer

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Current research status on poly ADP-ribose polymerase inhibitors and regulation of immunotherapy for patients with ovarian cancer