CD73抑制剂在肺癌免疫治疗中的研究进展
Research Progress of CD73 Inhibitors in Lung Cancer Immunotherapy
DOI: 10.12677/wjcr.2026.163019, PDF,   
作者: 张菀凌, 陈西敬*：中国药科大学基础医学与临床药学学院，江苏 南京
关键词: CD73；CD73抑制剂；肺癌；免疫耐药；临床研究；CD73； CD73 Inhibitor； Lung Cancer； Immune Drug Resistance； Clinical Research
摘要: 肺癌是全球发病率与死亡率最高的恶性肿瘤。免疫检查点阻断(Immune Checkpoint Blockade, ICB)已成为肺癌标准治疗方案之一，但大多数患者接受ICB时会出现原发或获得性耐药，这是制约治疗疗效与患者生存的关键瓶颈。研究证实，肿瘤免疫微环境抑制是ICB耐药的核心原因，CD73作为胞外腺苷生成的关键限速酶，可通过CD73-腺苷轴重塑免疫抑制微环境，且其在肺癌组织的高表达与疾病进展、复发及生存期缩短显著相关。因此，CD73抑制剂与ICB联用是解决该问题的重要方向。目前，CD73抑制剂主要分为单克隆抗体、小分子抑制剂及抗体偶联药物三类，临床研究显示，其与ICB合用可显著提升客观缓解率、改善耐药，与化疗构成的三联方案亦具良好前景，CD73与PD-L1共表达有望成为联合治疗疗效的潜在生物标志物。文章综述了CD73的生物学特性、抗肿瘤机制及肺癌临床研究进展，分析了相关生物标志物价值及临床挑战，以期为肺癌耐药的临床干预与基础研究提供参考。
Abstract: Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Immune checkpoint blockade (ICB) has established itself as one of the standard treatment modalities for lung cancer. However, the majority of patients exhibit primary or acquired drug resistance after undergoing ICB, which poses the key bottleneck constraining treatment efficacy and patient survival. It has been established that the suppression of the tumor immune microenvironment is the core cause of ICB resistance. CD73, as the crucial rate-limiting enzyme for extracellular adenosine production, is capable of reshaping the immunosuppressive microenvironment via the CD73-adenosine axis. Its high expression in lung cancer tissues is significantly associated with disease progression, recurrence, and reduced survival. Therefore, the combination of a CD73 inhibitor with ICB is an important approach to address this issue. Currently, CD73 inhibitors are primarily classified into three categories: monoclonal antibodies, small-molecule inhibitors, and antibody-drug conjugates. Clinical studies have demonstrated that the combination of CD73 and ICB can significantly enhance the objective response rate and overcome drug resistance. Triple therapy incorporating CD73 inhibition with PD-L1 blockade and chemotherapy also demonstrates significant potential. This article reviews the biological characteristics, anti-tumor mechanism, and clinical research progress of CD73 in lung cancer, analyzes the value and clinical challenges of related biomarkers, with the aim of providing references for clinical intervention and basic research on lung cancer drug resistance.
文章引用：张菀凌, 陈西敬. CD73抑制剂在肺癌免疫治疗中的研究进展[J]. 世界肿瘤研究, 2026, 16(3): 176-187. https://doi.org/10.12677/wjcr.2026.163019

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