Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8⁺ T cell-based immunophenotypic classification of this malignancy, followed by discussions of the preclinical data providing the basis to treat such immunophenotypes with combination immunotherapies. We posit that the integration of an accurate TME immunophenotype characterization with genetic data can enable the design of tailored therapeutic approaches and improve patient recruitment in clinical trials. Lastly, we propose a roadmap incorporating tissue-based profiling to guide future trials testing adoptive cell therapy approaches and assess novel immunotherapy combinations while promoting collaborative research.

尽管有书面证据表明卵巢癌细胞表达免疫检查点分子，例如 PD-1 和 PD-L1，并且肿瘤浸润淋巴细胞的存在与这种肿瘤类型患者的良好总生存期结果呈正相关，但迄今为止在这些患者中测试免疫检查点抑制剂 （ICI） 的试验结果令人失望。对 ICIs 缺乏反应可归因于肿瘤异质性以及与肿瘤微环境 （TME） 相关的固有或获得性耐药。了解肿瘤免疫生物学、发现用于患者选择的生物标志物和建立最佳治疗组合仍然是免疫疗法在卵巢癌中未来应用的关键挑战。在本综述中，我们总结了在卵巢癌患者中测试 ICIs 的试验结果。我们建议对这种恶性肿瘤实施基于 CD8 ⁺ T 细胞的系统免疫表型分类，然后讨论临床前数据，为用联合免疫疗法治疗此类免疫表型提供基础。我们认为，将准确的 TME 免疫表型特征与遗传数据相结合，可以设计量身定制的治疗方法并改善临床试验中的患者招募。最后，我们提出了一个路线图，其中包含基于组织的分析，以指导未来的试验测试过继细胞治疗方法并评估新的免疫疗法组合，同时促进合作研究。