随着免疫治疗尤其是免疫检查点抑制剂相关研究的深入,其在肝细胞癌(hepatocellular carcinoma,HCC)的综合治疗中得到了广泛的应用,目前已经成为中晚期HCC的一线治疗手段之一.鉴于HCC异质性和特征性的肿瘤微环境,仅有约20％的病人对免疫治疗敏感,大部分病人对单一免疫药物响应性较差,预后不佳.因此,利用HCC特征性的分子标志物对免疫治疗疗效进行响应性评估和动态监测,对于实现更加精准、个体化的HCC免疫治疗,增强药物响应性和改善预后,具有重要意义.目前研究较多的HCC分子标志物包括程序性死亡受体配体-1(programmed death ligand 1,PD-L1)、肿瘤突变负荷(tumor mutational burden,TMB)、错配修复基因缺陷(defect mismatch repair,dMMR)、微卫星不稳定(microsatellite instability,MSI)等,部分已在HCC免疫治疗响应性评估中表现出了良好预测价值.更重要的是,随着液体活检、基因检测技术的快速进步和广泛开展,新型分子标志物有望成为HCC免疫治疗响应性评估和预测的研究热点.此文结合近期HCC分子标志物在免疫治疗(以免疫检查点抑制剂为主)响应性评估中的应用和进展做一综述,旨在更加精准、个体化地指导HCC病人的免疫治疗,改善其预后.
Applications and outlooks of molecular biomarkers in immunotherapy of hepatocellular carcinoma
With the development of immunotherapy,especially in-depth exploration of immune checkpoint inhibitors(ICIs),it has been widely applied for managing advanced hepatocellular carcinoma(HCC).Regarding heterogeneity and specific tumor microenvironment of HCC,only about 20％of HCCs are sensitive to immunotherapy and most patients show a poor response to a single immune agent and thus have a poor prognosis.Thus it is imperative to predict and dynamically monitor the selected populations sensitive to immunotherapy with specific molecular biomarkers.More accurate and individualized immunotherapy of HCC may improve drug responsiveness and long-term prognosis.Currently several promising biomarkers of programmed death ligand 1(PD-L1),tumor mutational burden(TMB),defect mismatch repair(dMMR)and microsatellite instability(MSI)have been applied with mixed efficacies for immunotherapy of solid tumors.Furthermore,with rapid technical advancements of liquid biopsy and gene detection,novel molecular biomarkers are becoming the research focus of next-stage precise immunotherapy.This review summarized the latest applications of molecular biomarkers for prognostic evaluations of ICI-based immunotherapy for HCC.More precise and individualized immunotherapy shall further improve the long-term prognoses of patients with advanced HCC.
万方数据
维普
