Wang John S, Yassin Samer, Lin Adam Y
McGaw Medicine Center - Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Division of Hematology Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
J Immunother Cancer. 2025 Apr 24;13(4):e010603. doi: 10.1136/jitc-2024-010603.
The development of immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway has significantly transformed the landscape of cancer treatment. However, resistance mechanisms such as alternative immune checkpoints, T-cell exhaustion, low tumor burden, and immunosuppressive cells in the tumor microenvironment can limit therapeutic efficacy. Recent research has highlighted the role of tumor-derived exosomes expressing PD-L1, which may contribute to resistance by locally and systemically suppressing immune responses. Inhibiting exosome secretion has shown promise in enhancing the effectiveness of anti-PD-1/PD-L1 therapies. The therapeutic potential of targeting exosomes to improve PD-1/PD-L1 inhibition is gaining attention, with preclinical studies showing encouraging results. Clinical trials are needed to evaluate the combination of exosome secretion inhibitors with existing checkpoint therapies and provide hope for patients with resistant cancers.
靶向程序性细胞死亡蛋白1(PD-1)/程序性细胞死亡配体1(PD-L1)通路的免疫检查点抑制剂的发展显著改变了癌症治疗的格局。然而,诸如替代性免疫检查点、T细胞耗竭、低肿瘤负荷以及肿瘤微环境中的免疫抑制细胞等耐药机制会限制治疗效果。最近的研究突出了表达PD-L1的肿瘤来源外泌体的作用,其可能通过局部和全身抑制免疫反应而导致耐药。抑制外泌体分泌在增强抗PD-1/PD-L1疗法的有效性方面已显示出前景。靶向性外泌体以改善PD-1/PD-L1抑制的治疗潜力正受到关注,临床前研究显示出令人鼓舞的结果。需要开展临床试验来评估外泌体分泌抑制剂与现有检查点疗法的联合应用,并为耐药癌症患者带来希望。