中国HBV相关肝细胞癌与EBV相关鼻咽癌的免疫药理学进展：机制、治疗与临床展望

文献信息

中文摘要

背景： 致癌病毒仍然是中国癌症的重要病因，其中相当比例的恶性肿瘤由乙型肝炎病毒（HBV）和Epstein-Barr病毒（EBV）引起。HBV是中国肝细胞癌（HCC）的主要病因，约占85-92%的病例。EBV与非角化性未分化型鼻咽癌（NPC）密切相关，尤其是在流行区。方法：本综述概述了HBV相关HCC和EBV相关NPC中现有的免疫药理学，包括肿瘤免疫微环境如何被调控、免疫治疗的作用机制以及中国的主要临床进展。结果：手术、放疗和化疗等传统治疗方法效果并不十分理想，尤其是在疾病晚期，这凸显了纳入更有效治疗方法的必要性。免疫药理学干预已成为这方面的一项革命性实践。基于大规模临床试验，国产抗PD-1抗体（如信迪利单抗、卡瑞利珠单抗、替雷利珠单抗和特瑞普利单抗）已获得监管批准，目前用作不可切除HCC以及复发或转移性NPC的一线治疗。同时，使用EBV抗原的过继细胞疗法（包括EBV特异性细胞毒性T淋巴细胞和工程化T细胞受体策略）已显示出有前景的临床潜力。此外，免疫检查点阻断与靶向治疗或局部区域治疗的联合方案已显示出更好的生存率，尤其是在HBV感染者中。结论：尽管取得了这些改善，仍存在治疗耐药、免疫相关不良事件和生物标志物性能不一致等问题。未来的举措必须侧重于生物标志物指导的治疗决策、联合方案优化以及新型细胞疗法的更广泛临床应用。

英文摘要

Oncogenic viruses continue to be a significant cause of cancer in China, with a significant proportion of malignancies caused by hepatitis B virus (HBV) and Epstein-Barr virus (EBV). HBV is the dominant etiological factor for HCC in China, accounting for approximately 85-92% of cases. EBV is closely implicated in non-keratinizing undifferentiated nasopharyngeal carcinoma (NPC), especially in endemic areas. The use of conventional treatment methods, such as surgery, radiotherapy, and chemotherapy, has not been very effective, especially at advanced stages of the disease, underscoring the need to incorporate more effective treatment approaches. Immunopharmacological interventions have emerged as a revolutionary practice in this regard. This review provides an overview of existing immunopharmacology in HBV-related HCC and EBV-associated NPC, including how the tumour immune microenvironment is modulated, the mechanisms of action of immune-based therapies, and the major clinical advances in China. Domestically developed anti-PD-1 antibodies, such as sintilimab, camrelizumab, tislelizumab, and toripalimab, have received regulatory approval based on large-scale clinical trials and are currently used as first-line treatment for unresectable HCC and for recurrent or metastatic NPC. Simultaneously, adoptive cellular therapies using EBV antigens (including EBV-specific cytotoxic T lymphocytes and engineered T-cell receptor strategies) have shown promising clinical potential. Moreover, combination regimens with immune checkpoint blockade and targeted therapies or locoregional therapies have demonstrated better survival rates, especially in HBV-infected people. Despite these improvements, there are still issues, such as therapeutic resistance, immune-related adverse events, and inconsistent biomarker performance. Future initiatives must focus on biomarker-directed treatment decisions, combination regimen optimization, and the wider clinical use of new cellular therapies.