肝细胞肝癌免疫检查点阻断治疗疗效相关生物标志物的研究进展

Research advances of biomarkers related to the efficacy of immune checkpoint blockade therapy for hepatocellular carcinoma

目的总结与肝细胞肝癌(HCC)免疫检查点抑制剂治疗疗效相关的生物标志物。方法查阅并总结以靶向程序性死亡受体1及其配体1(PD-1/PD-L1)通路抑制剂为主的免疫检查点抑制剂单药治疗,以及其与靶向药物联合治疗的相关生物标志物的基础和临床应用研究文献,并加以综述。结果免疫治疗与靶向治疗的联合方案为晚期HCC患者的治疗带来了希望,但仍有一部分患者不能临床获益。目前研究表明,肿瘤组织中PD-L1表达、肿瘤突变负荷、肿瘤浸润淋巴细胞、外周免疫细胞、循环肿瘤DNA、肠道微生物菌群等均对HCC的免疫治疗或靶向联合免疫治疗疗效有一定的预测作用。结论目前尚无明确的生物标志物能预测HCC免疫治疗及其联合方案的疗效,仍需要更多的前瞻性研究来证实这些生物标志物的预测价值,并建立一个多因素预测模型或免疫评分来筛选可能获益的患者,这对HCC的精准免疫治疗具有重要意义。

Objective To summarize the biomarkers related to the efficacy of immune checkpoint inhibitors for hepatocellular carcinoma(HCC). Method Reviewed and summarized the literatures on the basic and clinical application of biomarkers related to programmed cell death protein 1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors and their combination with targeted therapy. Results The combination of immunotherapy and targeted therapy had brought great hope for the treatment of patients with advanced HCC, but there were still some patients who could not benefit from it. Recent studies had shown that expression of PD-L1 in tumor tissue, tumor mutational burden, tumor-infiltrating lymphocytes, peripheral immune cells, circulating tumor DNA, gut microbiome, and so on, could predict the efficacy of immunotherapy or targeted therapy combined with immunotherapy for HCC. Conclusions There is no specific biomarker to predict the efficacy of immunotherapy and its combination regimen for HCC. More prospective studies are needed to confirm the predictive value of these biomarkers and to establish a multi-factor predictive model or immune score to screen patients who may benefit, which is of great significance for precise immunotherapy of HCC.