Sun Qiyue, Hong Senlian
State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Int J Mol Sci. 2025 Jan 31;26(3):1238. doi: 10.3390/ijms26031238.
Immune checkpoint blockade therapy, represented by anti-PD-1/PD-L1 monoclonal antibodies, has significantly changed the immunotherapy landscape. However, the treatment is still limited by unsatisfactory response rates, immune-related adverse effects, and drug resistance. Current studies have established that glycosylation, a common post-translational modification, is crucial in promoting cancer progression and immune invasion. Targeting aberrant glycosylation in cancers presents precision medicine regimens for monitoring cancer progression and developing personalized medicine. Notably, the immune checkpoints PD-1 and PD-L1 are highly glycosylated, which affects PD-1/PD-L1 interaction and the binding of anti-PD-1/PD-L1 monoclonal antibodies. Recent achievements in glycoscience to enhance patient outcomes, referred to as glycotherapy, have underscored their high potency in advancing PD-1/PD-L1 blockade therapies, i.e., glycoengineered antibodies with improved binding toward PD-1/PD-L1, pharmaceutic inhibitors for core fucosylation and sialylation, and synergistic treatment with the antibody-sialidase conjugate. This review briefly introduces the PD-1/PD-L1 axis and glycosylation and highlights the fundamental and applied advances in glycoscience that improve PD-1/PD-L1 immunoblockade therapies.
以抗PD-1/PD-L1单克隆抗体为代表的免疫检查点阻断疗法显著改变了免疫治疗格局。然而，该治疗仍受到应答率不理想、免疫相关不良反应和耐药性的限制。目前的研究已经确定，糖基化作为一种常见的翻译后修饰，在促进癌症进展和免疫侵袭方面至关重要。针对癌症中异常糖基化的研究为监测癌症进展和开发个性化药物提供了精准医疗方案。值得注意的是，免疫检查点PD-1和PD-L1高度糖基化，这会影响PD-1/PD-L1相互作用以及抗PD-1/PD-L1单克隆抗体的结合。糖科学领域在改善患者预后方面的最新成果，即糖疗法，凸显了其在推进PD-1/PD-L1阻断疗法方面的高效性，例如对PD-1/PD-L1具有更好结合能力的糖工程化抗体、核心岩藻糖基化和唾液酸化的药物抑制剂，以及与抗体 - 唾液酸酶偶联物的联合治疗。本综述简要介绍了PD-1/PD-L1轴和糖基化，并强调了糖科学在改善PD-1/PD-L1免疫阻断疗法方面的基础和应用进展。
