Dickinson Kaitlyn, Yee Elliott J, Vigil Isaac, Schulick Richard D, Zhu Yuwen
Department of Surgery, Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cancer Immunol Immunother. 2024 Oct 3;73(12):253. doi: 10.1007/s00262-024-03801-7.
Although immune checkpoint blockade (ICB) has become the mainstay of treatment for advanced solid organ malignancies, success in revitalizing the host anticancer immune response remains limited. G-protein coupled receptors (GPCRs) are a broad family of cell-surface proteins that have been regarded as main players in regulating the immune system, namely by mediating the activity of T lymphocytes. Among the most novel immunoregulatory GPCRs include GPR171, lysophosphatidic acid receptors (LPARs), GPR68, cannabinoid receptor 2 (CB2), and prostaglandin E receptors, many of which have shown promise in mediating antitumor response via activation of cytotoxic T cells, inhibiting immunosuppressive lymphocytes, and facilitating immune cell infiltration within the tumor microenvironment across multiple types of cancers. This paper reviews our current understanding of some of the most novel GPCRs-their expression patterns, evolving roles within the immune system and cancer, potential therapeutic applications, and perspective for future investigation.
尽管免疫检查点阻断（ICB）已成为晚期实体器官恶性肿瘤治疗的主要手段，但在重振宿主抗癌免疫反应方面的成效仍然有限。G蛋白偶联受体（GPCRs）是一类广泛的细胞表面蛋白家族，被认为是调节免疫系统的主要参与者，即通过介导T淋巴细胞的活性来发挥作用。最新的免疫调节性GPCRs包括GPR171、溶血磷脂酸受体（LPARs）、GPR68、大麻素受体2（CB2）和前列腺素E受体，其中许多在介导抗肿瘤反应方面显示出前景，具体方式包括激活细胞毒性T细胞、抑制免疫抑制性淋巴细胞以及促进多种癌症类型肿瘤微环境内的免疫细胞浸润。本文综述了我们目前对一些最新的GPCRs的理解——它们的表达模式、在免疫系统和癌症中不断演变的作用、潜在的治疗应用以及未来研究的前景。
