Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne (UNIL), Lausanne, Switzerland.
Nat Rev Clin Oncol. 2024 Nov;21(11):801-817. doi: 10.1038/s41571-024-00937-4. Epub 2024 Sep 4.
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.
尽管有文献记载表明卵巢癌细胞表达免疫检查点分子，如 PD-1 和 PD-L1，并且肿瘤浸润淋巴细胞的存在与这类肿瘤患者的总体生存结局呈正相关，但迄今为止，在这些患者中测试免疫检查点抑制剂 (ICI) 的临床试验结果令人失望。ICI 无应答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性。了解肿瘤免疫生物学、发现患者选择的生物标志物以及建立最佳治疗组合仍然是未来在卵巢癌中应用免疫疗法的希望，但也是一个关键挑战。在这篇综述中，我们总结了在卵巢癌患者中测试 ICI 的临床试验结果。我们提出了对这种恶性肿瘤进行基于 CD8 T 细胞的免疫表型分类的系统实施，随后讨论了为用联合免疫疗法治疗这种免疫表型提供基础的临床前数据。我们假设将准确的 TME 免疫表型特征与遗传数据相结合，可以设计出针对特定患者的治疗方法，并提高临床试验中患者的招募率。最后，我们提出了一个路线图，纳入基于组织的分析，以指导未来的临床试验，测试过继细胞治疗方法，并评估新的免疫治疗组合，同时促进合作研究。
