Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, MD 21205, USA.
Cytokine Growth Factor Rev. 2024 Feb;75:93-100. doi: 10.1016/j.cytogfr.2023.10.002. Epub 2023 Oct 6.
Uterine fibroids (UF), also called uterine leiomyoma, is one of the most prevalent uterine tumors. UF represents a serious women's health global problem with a significant physical, emotional, and socioeconomic impact. Risk factors for UF include racial disparities, age, race, hormonal factors, obesity, and lifestyle (diet, physical activity, and stress. There are several biological contributors to UF pathogenesis such as cellular proliferation, angiogenesis, and extracellular matrix (ECM) accumulation. This review addresses tumor immune microenvironment as a novel mediator of ECM deposition. Polarization of immune microenvironment towards the immunosuppressive phenotype has been associated with ECM deposition. Immunosuppressive cells include M2 macrophage, myeloid-derived suppressor cells (MDSCs), and Th17 cells, and their secretomes include interleukin 4 (IL-4), IL-10, IL-13, IL-17, IL-22, arginase 1, and transforming growth factor-beta (TGF-β1). The change in the immune microenvironment not only increase tumor growth but also aids in collagen synthesis and ECM disposition, which is one of the main hallmarks of UF pathogenesis. This review invites further investigations on the change in the UF immune microenvironment as well as a novel targeting approach instead of the traditional UF hormonal and supportive treatment.
子宫肌瘤(UF),也称为子宫平滑肌瘤,是最常见的子宫肿瘤之一。UF 是一个严重的全球妇女健康问题,对身体、情感和社会经济都有重大影响。UF 的风险因素包括种族差异、年龄、种族、激素因素、肥胖和生活方式(饮食、体育活动和压力)。UF 的发病机制有几个生物学因素,如细胞增殖、血管生成和细胞外基质(ECM)积累。这篇综述探讨了肿瘤免疫微环境作为 ECM 沉积的一种新的介质。免疫微环境向免疫抑制表型的极化与 ECM 沉积有关。免疫抑制细胞包括 M2 巨噬细胞、髓系来源的抑制细胞(MDSCs)和 Th17 细胞,它们的分泌因子包括白细胞介素 4(IL-4)、白细胞介素 10(IL-10)、白细胞介素 13(IL-13)、白细胞介素 17(IL-17)、白细胞介素 22(IL-22)、精氨酸酶 1 和转化生长因子-β(TGF-β1)。免疫微环境的改变不仅增加了肿瘤的生长,而且有助于胶原蛋白的合成和 ECM 的分布,这是 UF 发病机制的主要特征之一。这篇综述邀请进一步研究 UF 免疫微环境的变化以及一种新的靶向方法,而不是传统的 UF 激素和支持性治疗。