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.