Conforti Fabio, Pala Laura, Di Mitri Diletta, Catania Chiara, Cocorocchio Emilia, Laszlo Daniele, Ceresoli Giovanni, Locatelli Marzia, Facella Flaminia, De Pas Tommaso, Rambaldi Benedetta, Rambaldi Alessandro, Viale Giuseppe, Bagnardi Vincenzo, Giaccone Giuseppe, Mantovani Alberto
Division of Medical Oncology, Humanitas Gavazzeni, Bergamo, Italy; Humanitas University, Milan, Italy.
Division of Medical Oncology, Humanitas Gavazzeni, Bergamo, Italy; Tumor Microenviroment Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Cancer Cell. 2025 Mar 10;43(3):343-360. doi: 10.1016/j.ccell.2025.02.013.
Sex-based differences have been observed in the incidence and prognosis of various cancers, as well as in the response to immune check point inhibitors (ICIs). These disparities are partially attributed to sex-based differences in the molecular characteristics of the anticancer immune response, which are largely influenced by sex hormones. Here, we provide a comprehensive overview on how sex hormones affect innate and adaptive immunity and contribute to shaping the features of tumor immune microenvironment and response to anticancer immunotherapy. We also discuss the promising potential and challenges of combining sex hormone manipulation with anticancer immunotherapy as new therapeutic strategy. We surmise that a sex-based perspective should be part of precision medicine approaches, and sex hormones manipulation provides opportunities for innovative immune therapeutic approaches.
在各种癌症的发病率和预后以及对免疫检查点抑制剂（ICI）的反应中均观察到了基于性别的差异。这些差异部分归因于抗癌免疫反应分子特征的性别差异，而这在很大程度上受性激素影响。在此，我们全面概述了性激素如何影响先天性和适应性免疫，并有助于塑造肿瘤免疫微环境的特征以及对抗癌免疫治疗的反应。我们还讨论了将性激素调控与抗癌免疫治疗相结合作为新治疗策略的潜在前景和挑战。我们推测，基于性别的观点应成为精准医学方法的一部分，而性激素调控为创新免疫治疗方法提供了机会。
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