G蛋白偶联雌激素受体在免疫调节中作用的研究进展
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作者单位:

1.江西省肿瘤医院 乳腺肿瘤外科,江西 南昌 330029;2.南昌大学研究生院 医学部,江西 南昌 330031;3.江西省恶性肿瘤临床医学研究中心,江西 南昌 330029;4.吉安市中心人民医院 急诊外科,江西 吉安 343000;5.南昌大学抚州医学院,江西 抚州 344000

作者简介:

曾小强,江西省肿瘤医院硕士研究生,主要从事乳腺疾病临床及基础方面的研究。

基金项目:

国家自然科学基金资助项目(82160565);江西省自然科学基金资助项目(20212BAB216063);江西省科学技术厅青年人才基金资助项目(20232BCJ23035)。


Role of G protein-coupled estrogen receptor in immunomodulation: a review of research progress
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1.Department of Breast Surgical Oncology, Jiangxi Cancer Hospital, Nanchang 330029, China;2.Medical Department of Graduate School, Nanchang University, Nanchang 330031, China;3.Jiangxi Clinical Research Center for Cancer, Nanchang 330029, China;4.Department of Emergency Surgery, Ji'an Central People's Hospital, Ji'an, Jiangxi 343000, China;5.Fuzhou Medical Collage of Nanchang University, Fuzhou, Jiangxi 344000, China

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    摘要:

    近年来研究发现,G蛋白偶联雌激素受体(GPER)不同于传统的核受体,是第三种独立作用的雌激素受体,它属于七次跨膜的G蛋白偶联受体(GPCR)家族成员。雌激素通过GPER介导G蛋白信号通路活化从而在正常生理及多种异常疾病中扮演重要角色,包括癌症、心血管疾病和炎症性疾病等。GPER表达于多种免疫细胞中,通过增强免疫细胞活性或调节免疫细胞之间的互动从而在免疫反应中发挥作用。同样,GPER还可参与炎症因子相关基因的表达从而抑制炎症反应。近期研究进一步揭示GPER不仅参与正常免疫系统的维持、异常免疫性疾病及炎症性病变,而且在肿瘤免疫调节中或有重要价值。笔者研究团队前期在多种恶性肿瘤中证实GPER介导的下游信号通路及其生物学功能,并发现GPER在乳腺癌和肝癌的肿瘤微环境中可能通过能量代谢重塑调节肿瘤免疫,以及血液肿瘤免疫治疗中靶向GPER有协同抗肿瘤药物的正向作用。综合现有研究发现,GPER可通过多样化的调节方式参与多种癌症的肿瘤免疫过程,包括乳腺癌中GPER通过调节免疫检查点分子的表达影响肿瘤免疫逃逸;肝癌中GPER调节免疫微环境和免疫细胞浸润,增加细胞因子和趋化因子的产生影响肿瘤免疫调节;结直肠癌中GPER增强免疫细胞的抗肿瘤活性和促进免疫细胞的细胞毒杀伤能力;血液肿瘤中GPER影响不同免疫细胞之间的“交叉对话”增强抗肿瘤免疫治疗等。因此,GPER为免疫相关疾病的治疗发展提供了新的途径,尽管目前尚处于探索阶段,但GPER作为新靶点联合免疫检查点抑制剂等药物的研发充满了临床潜力。本文综述当前GPER相关免疫调节作用的研究进展,为相关的基础与临床研究提供参考。

    Abstract:

    In recent years, studies have found that G protein-coupled estrogen receptor (GPER), distinct from traditional nuclear receptors, is a third independent estrogen receptor that belongs to the family of seven-transmembrane G protein-coupled receptors (GPCRs). Estrogen activates G protein signaling pathways through GPER, playing important roles in normal physiology and various pathological conditions, including cancer, cardiovascular diseases, and inflammatory diseases. GPER is expressed in various immune cells and plays a role in immune responses by enhancing immune cell activity or modulating interactions between immune cells. Additionally, GPER can participate in the expression of inflammatory factor-related genes, thereby inhibiting inflammatory responses. Recent studies have further revealed that GPER is not only involved in maintaining normal immune system function, abnormal immune diseases, and inflammatory diseases but also may have important value in tumor immune regulation. The authors' research team has previously confirmed the downstream signaling pathways mediated by GPER and its biological functions in various malignant tumors, and have found that GPER may regulate tumor immunity of breast and liver cancer through energy metabolism remodeling in the tumor microenvironment, and targeting GPER in hematologic tumor immune therapy has a synergistic effect with anti-tumor drugs. Based on existing research findings, GPER participates in tumor immune processes of various cancers in diverse ways. For example, in breast cancer, GPER affects tumor immune escape by regulating the expression of immune checkpoint molecules; in liver cancer, GPER regulates the immune microenvironment and immune cell infiltration, affecting tumor immune regulation by increasing the production of cytokines and chemokines; in colorectal cancer, GPER enhances the anti-tumor activity of immune cells and promotes the cytotoxicity of immune cells; in hematologic tumors, GPER influences the "cross-talk" between different immune cells, enhancing anti-tumor immune therapy, etc. Therefore, GPER provides a new avenue for the development of immune-related diseases treatments. Although it is still in the exploratory stage, the development of GPER as a new target combined with immune checkpoint inhibitors and other drugs is full of clinical potential. This article reviews the current research progress on the immune regulatory effects of GPER, to provide a reference for related basic and clinical research.

    图1 GPER在多种肿瘤免疫调节中的功能Fig.1 GPER functions in immunomodulation of multiple tumors
    图1 GPER在多种肿瘤免疫调节中的功能Fig.1 GPER functions in immunomodulation of multiple tumors
    表 1 Ⅰ~Ⅳ型超敏反应中GPER介导的相关免疫细胞、免疫因子功能变化Table 1 Functional changes of related immune cells and immune factors mediated by GPER in type Ⅰ-Ⅳ hypersensitivity reactions
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曾小强,周菁,黄晏骁,徐佳伟,徐家乐,余腾骅. G蛋白偶联雌激素受体在免疫调节中作用的研究进展[J].中国普通外科杂志,2024,33(5):840-847.
DOI:10.7659/j. issn.1005-6947.2024.05.017

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  • 收稿日期:2023-06-20
  • 最后修改日期:2023-10-17
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  • 在线发布日期: 2024-06-06