Wang Tiecheng, Jin Jiakang, Qian Chao, Lou Jianan, Lin Jinti, Xu Ankai, Xia Kaishun, Jin Libin, Liu Bing, Tao Huimin, Yang Zhengming, Yu Wei
Department of Orthopedics, Shengzhou People's Hospital, #666 Dangui Road, Shengzhou, 312400, Zhejiang, People's Republic of China.
Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China.
Cancer Cell Int. 2021 Jun 7;21(1):295. doi: 10.1186/s12935-021-02003-w.
As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.
作为重要的性激素，雌激素及其受体已被证明参与自身免疫性疾病和抗肿瘤免疫的调节。肿瘤免疫的调节与癌细胞、免疫细胞和肿瘤微环境之间的相互作用有关，所有这些都被认为是雌激素诱导免疫系统调节的潜在靶点。然而，雌激素诱导免疫的具体机制尚不清楚。通常，雌激素会导致雌激素/雌激素受体复合物的核定位，并改变靶基因的转录模式，从而导致肿瘤细胞重编程和免疫细胞分化。然而，雌激素诱导的非经典信号通路激活对雌激素的快速作用也至关重要，如NF-κB、MAPK-ERK和β-连环蛋白通路的激活，这一点尚未完全阐明。因此，以这两种方式研究雌激素调节机制对肿瘤免疫至关重要，并可为内分泌激素靶向癌症免疫治疗提供潜力。在此，本综述总结了雌激素诱导的经典和非经典信号转导通路，旨在聚焦雌激素与癌症免疫以及免疫相关肿瘤微环境调节之间的关系。这些临床前研究结果表明，雌激素靶向治疗具有癌症免疫治疗的应用前景，这需要对这些治疗策略进行进一步的转化研究。
