Dholakia Jhalak, Scalise Carly, Arend Rebecca C
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cancers (Basel). 2021 Apr 2;13(7):1694. doi: 10.3390/cancers13071694.
Gynecologic malignancies are increasing in incidence, with a plateau in clinical outcomes necessitating novel treatment options. Immunotherapy and modulation of the tumor microenvironment are rapidly developing fields of interest in gynecologic oncology translational research; examples include the PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) axes and the Wnt pathway. However, clinical successes with these agents have been modest and lag behind immunotherapy successes in other malignancies. A thorough contextualization of preclinical models utilized in gynecologic oncology immunotherapy research is necessary in order to effectively and efficiently develop translational medicine. These include murine models, in vitro assays, and three-dimensional human-tissue-based systems. Here, we provide a comprehensive review of preclinical models for immunotherapy in gynecologic malignancies, including benefits and limitations of each, in order to inform study design and translational research models. Improved model design and implementation will optimize preclinical research efficiency and increase the translational value to positive findings, facilitating novel treatments that improve patient outcomes.
妇科恶性肿瘤的发病率正在上升，临床治疗效果趋于平稳，这就需要新的治疗方案。免疫疗法和肿瘤微环境的调节是妇科肿瘤转化研究中迅速发展的热门领域；例如程序性死亡蛋白1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）信号轴以及Wnt信号通路。然而，这些药物在临床上取得的成功并不显著，落后于其他恶性肿瘤的免疫治疗成果。为了有效且高效地开展转化医学，有必要对妇科肿瘤免疫治疗研究中使用的临床前模型进行全面的背景分析。这些模型包括小鼠模型、体外试验以及基于三维人体组织的系统。在此，我们对妇科恶性肿瘤免疫治疗的临床前模型进行全面综述，包括每种模型的优缺点，以便为研究设计和转化研究模型提供参考。改进模型设计与实施将优化临床前研究效率，并提高阳性结果的转化价值，推动能改善患者预后的新疗法的发展。
