肿瘤免疫治疗新靶标PGE_(2)受体EP4的研究进展

Research progress of PGE_(2) receptor EP4,a new target of cancer immunotherapy

肿瘤免疫治疗已成为人们对抗癌症的重要手段,但响应率低仍是目前亟需解决的关键问题。大量研究表明,逆转肿瘤免疫抑制是阻断肿瘤免疫逃逸、增强和扩大免疫疗法疗效的重要策略。前列腺素E_(2)(PGE_(2))是肿瘤微环境中的强效免疫介质,可特异性结合细胞膜上的七次跨膜蛋白EP4受体,诱导肿瘤微环境免疫抑制,驱动肿瘤免疫逃逸。特异性阻断PGE_(2)/EP4信号通路可有效解除肿瘤微环境免疫抑制,增强抗肿瘤免疫反应,促进肿瘤消退。本文从EP4受体的结构、信号转导、调控机制及其拮抗剂开发现状等方面阐述了EP4受体在肿瘤免疫治疗领域的新进展和新发现,并展望了新的发展方向。

Cancer immunotherapy has revolutionized the cancer treatment paradigm,but low response rate is still a key issue that needs to be addressed urgently.Numerous studies have shown that targeting tumor immunosuppression is an ef-fective strategy to block tumor immune escape,enhance and expand the efficacy of immunotherapy.Prostaglandin E_(2)(PGE_(2))is a potent immune mediator in the tumor microenvironment(TME),which can specifically bind to the seven-transmem-brane protein EP4 receptor,thereby inducing immune suppression in TME and promoting tumor immune escape.Targeting the PGE_(2)/EP4 pathway is considered to be an effective strategy to relieve TME immunosuppression,thereby enhancing an-ti-tumor immune responses and promoting tumor regression.This review summarized the research progress of EP4 receptor in cancer immunotherapy from the aspects of structure,signal transduction,regulatory mechanism,and drug discovery.