Wang Xu, Li Lanying, Liu Dan, Jin Yuhang, Zhao Xuan, Li Sijin, Hou Rui, Guan Zhangchun, Ma Wen, Zheng Junnian, Lv Ming, Shi Ming
Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu 221002, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
College of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
Biochem Pharmacol. 2025 Mar;233:116762. doi: 10.1016/j.bcp.2025.116762. Epub 2025 Jan 20.
Immune checkpoints are critical for maintaining autoimmune homeostasis and are implicated in various autoimmune diseases, with their significance increasingly recognized. Investigating the functions and mechanisms of these checkpoints is essential for the development of more effective treatments. Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) stands out as a unique immune checkpoint, with limited expression in most normal tissues but prominent presence in various hematological and solid tumors. It is also expressed on numerous immune and stromal cells, functioning as both a "Tumor Immune Checkpoint" and a "Tumor Stromal Immune Checkpoint." Due to its distinct expression profile, LILRB4 plays a pivotal role in tumors, autoimmune diseases, allergic reactions, and the maintenance of immune homeostasis during transplantation and pregnancy. A thorough understanding of its ligands, functions, mechanisms, and ongoing therapeutic strategies targeting LILRB4 will be crucial for the development of advanced therapeutic options. This review examines LILRB4 expression and function across multiple diseases and discusses therapeutic approaches targeting LILRB4 in various contexts. Additionally, the potential of combining current drugs with LILRB4-targeted therapies is explored. Challenges in developing LILRB4-targeting drugs are also addressed, offering valuable insights for future research.
免疫检查点对于维持自身免疫稳态至关重要，且与多种自身免疫性疾病相关，其重要性日益得到认可。研究这些检查点的功能和机制对于开发更有效的治疗方法至关重要。白细胞免疫球蛋白样受体B4（LILRB4）作为一种独特的免疫检查点脱颖而出，在大多数正常组织中表达有限，但在各种血液系统肿瘤和实体瘤中显著存在。它也在众多免疫细胞和基质细胞上表达，兼具“肿瘤免疫检查点”和“肿瘤基质免疫检查点”的功能。由于其独特的表达谱，LILRB4在肿瘤、自身免疫性疾病、过敏反应以及移植和妊娠期间免疫稳态的维持中发挥着关键作用。全面了解其配体、功能、机制以及针对LILRB4的现有治疗策略对于开发先进的治疗方案至关重要。本综述探讨了LILRB4在多种疾病中的表达和功能，并讨论了在不同情况下针对LILRB4的治疗方法。此外，还探索了将现有药物与LILRB4靶向疗法相结合的潜力。同时也讨论了开发LILRB4靶向药物面临的挑战，为未来研究提供了有价值的见解。
