免疫检查点抑制剂治疗肝细胞癌的研究进展

Research progress on immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

肝癌的发病率及死亡率在全球恶性肿瘤中均位居前列。初诊的肝细胞癌(hepatocellular carcinoma,HCC)患者大多已处于晚期,失去手术根治的机会,全身治疗成为主要的治疗手段。随着免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的出现,多种ICIs被批准用于晚期HCC患者,ICIs联合抗血管生成药物为主的靶向药物的治疗方案也被证实比ICIs单药效果更佳。但是,无论是单药ICIs还是联合治疗方案,多数患者仍不能从中获益。根据患者治疗的不同目标,通过肿瘤标记物选择不同的治疗方案是目前临床面临的挑战。本文对目前ICIs以及联合不同药物和局部治疗在HCC的临床研究进展、预测疗效和预后的生物标记物以及耐药性相关问题进行综述。

The incidence and mortality rates of liver cancer are among the highest reported for malignant tumors worldwide.Most patients with hepatocellular carcinoma(HCC)present with advanced stage disease at initial diagnosis,which precludes the option of radical surgery.Systemic therapy is the main treatment option for such patients.In recent years,a variety of immune checkpoint inhibitors(ICIs)have emerged and have been approved for use in advanced HCC.ICIs in combination with anti-angiogenic agents have been shown to be more effective than ICIs alone.However,most patients still cannot benefit from either ICI monotherapy or the combination of ICIs and anti-angiogenic agents.The choice of the appropriate treatment,according to the specific treatment goals for each patient,and of different biomarkers is one of the current challenges in clinical practice.In this review,we summarize the current state of research on the use of ICIs alone and ICI-based combination therapies using different drugs and local therapies,the use of biomarkers for predicting the efficacy of therapy and patient prognosis,and drug resistance to ICIs alone and ICI-based combination therapies.