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高级别浆液性卵巢癌的免疫治疗进展:从前景到实践

英文原题:Immunotherapy advancements in high-grade serous ovarian cancer: From promise to practice.

PubMed 2026/04/01(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

研究概要

高级别浆液性卵巢癌(HGSC)是最常见的上皮性卵巢癌亚型,复发率高,总生存期差。

中文摘要

高级别浆液性卵巢癌(HGSC)是最常见的上皮性卵巢癌亚型,复发率高,总生存期差。尽管在肿瘤细胞减灭术、铂类化疗和聚(ADP-核糖)聚合酶(PARP)抑制剂方面取得了进展,但治疗结局仍然不佳,凸显了对新方法的需求。免疫治疗目前是多种实体瘤管理的标准治疗,但其在HGSC中的作用仍在逐步明确。本综述综合了关于HGSC免疫景观、预测性生物标志物、耐药机制以及治疗策略的当前证据,包括免疫检查点抑制剂、疫苗、过继性细胞疗法、溶瘤病毒以及与免疫系统相互作用的抗体药物偶联物(ADCs)。虽然检查点阻断在未经选择的人群中显示出适度疗效,但靶向叶酸受体α(FRα)和滋养层细胞表面抗原2(TROP2)的ADCs已显示出最令人鼓舞的临床结果。同源重组缺陷、程序性细胞死亡蛋白配体1(PD-L1)表达、肿瘤突变负荷和新抗原负荷等生物标志物可能有助于患者选择,尽管尚无一种在免疫治疗中得到完全验证。与PARP抑制剂、抗血管生成药物或化疗的联合方案具有潜在协同作用,但最佳序贯方案仍未确定。毒性管理至关重要,因为免疫相关不良事件虽然通常可控,但可能与其他全身治疗的不良反应重叠。多学科方法和患者教育是安全整合的关键。总体而言,免疫治疗对选定的HGSC患者代表了一条有前景的途径。ADCs引领着当前的临床进展。未来的优先事项包括生物标志物驱动的试验设计、战略性治疗序贯以及创新联合策略,以在最大化治疗获益的同时最小化毒性。

展开英文摘要原文

High-grade serous ovarian carcinoma (HGSC) is the most common epithelial ovarian cancer subtype, with high recurrence rates and poor overall survival. Despite progress with cytoreductive surgery, platinum-based chemotherapy, and poly(ADP-ribose) polymerase (PARP) inhibitors, treatment outcomes remain poor, underscoring the need for novel approaches. Immunotherapy is currently the standard of care for the management of several solid tumors, but its role in HGSC is still emerging. This review synthesizes current evidence on the immune landscape of HGSC, predictive biomarkers, resistance mechanisms, and therapeutic strategies including immune checkpoint inhibitors, vaccines, adoptive cell therapies, oncolytic viruses, and antibody-drug conjugates (ADCs) which interact with the immune system. While checkpoint blockade has demonstrated modest efficacy in unselected populations, ADCs targeting folate receptor alpha (FRα) and trophoblast cell-surface antigen 2 (TROP2) have shown the most encouraging clinical results. Biomarkers such as homologous recombination deficiency, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutational burden, and neoantigen load may enable patient selection, although none are fully validated for immunotherapies. Combination regimens with PARP inhibitors, anti-angiogenic agents, or chemotherapy offer potential synergy, but optimal sequencing remains undefined. Toxicity management is essential, as immune-related adverse events, although generally manageable, may overlap with the side effects of other systemic therapies. Multidisciplinary approaches and patient education are key to safe integration. Overall, immunotherapy represents a promising avenue for selected patients with HGSC. ADCs are leading current clinical advances. Future priorities include biomarker-driven trial designs, strategic treatment sequencing, and innovative combination strategies to maximize therapeutic benefit while minimizing toxicity.

论文信息

作者
Heidinger M、Caruso G、Coelho R、Stiegeler N、Petousis S、Kacperczyk-Bartnik J、Oseledchyk A、Jacob F
第一作者单位
Gynaecological Cancer Centre, University Hospital Basel, Basel 4056, Switzerland.Switzerland
通讯作者单位
Gynaecological Cancer Centre, University Hospital Basel, Basel 4056, Switzerland; Department of Biomedicine, University Hospital and University of Basel, Basel 4056, Switzerland; Peter MacCallum Cancer Center, East Melbourne, Victoria 3002, Australia. Electronic address: tibor.zwimpfer@unibas.ch.Switzerland
文献类型
综述
期刊
Critical reviews in oncology/hematology2026 Jul
原文标识
PubMed 41933852 · DOI 10.1016/j.critrevonc.2026.105312