卵巢癌的免疫治疗:采用基于免疫表型的定制方法。
Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach.
发表日期:2024 Sep 04
作者:
Eleonora Ghisoni, Matteo Morotti, Apostolos Sarivalasis, Alizée J Grimm, Lana Kandalaft, Denarda Dangaj Laniti, George Coukos
来源:
Nature Reviews Clinical Oncology
摘要:
尽管有记录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良好的总体生存结果之间存在正相关,但结果迄今为止,在这些患者中测试免疫检查点抑制剂(ICIs)的试验令人失望。对 ICI 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性。了解肿瘤免疫生物学、发现用于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免疫疗法在卵巢癌中应用的希望,但也是一个关键挑战。在这篇综述中,我们总结了卵巢癌患者 ICI 试验的结果。我们建议对这种恶性肿瘤实施基于 CD8 T 细胞的系统性免疫表型分类,然后讨论临床前数据,为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 免疫表型表征与遗传数据相结合,可以设计出量身定制的治疗方法,并改善临床试验中的患者招募。最后,我们提出了一个结合基于组织的分析的路线图,以指导未来测试过继细胞治疗方法的试验并评估新型免疫治疗组合,同时促进合作研究。© 2024。Springer Nature Limited。
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.© 2024. Springer Nature Limited.