基于TumorFisher CTC检测探讨PD-1/PD-L1免疫抑制剂治疗肝细胞癌的效果

摘要/Abstract

摘要： 目的基于TumorFisher 循环肿瘤细胞(CTC)检测探讨程序性死亡受体1/程序性死亡受体-配体1(PD-1/PD-L1)免疫抑制剂治疗肝细胞癌(HCC)的效果。方法选取盐城市人民医院2021年8月至2022年12月收治的120例中晚期HCC患者,分为两组各60例。对照组采用药物微球经肝动脉化疗栓塞(DEB-TACE)联合酪氨酸激酶抑制剂(TKI)治疗,观察组加用PD-1/PD-L1免疫抑制剂治疗。比较两组肿瘤反应、TumorFisher CTC检测结果和血清血管内皮生长因子受体(VEGF)、基质金属蛋白酶-9(MMP-9)水平、不良反应,并随访无进展生存期(PFS)和总生存期(OS)。结果观察组客观缓解率(ORR)和疾病控制率(DCR)高于对照组,分别为71.6%(43/60)比53.33%(32/60)、81.67%(49/60)比63.33%(38/60),差异有统计学意义(P<0.05)。治疗后,两组总CTC数、总PD-L1⁺CTC数和血清VEGF、MMP-9水平均下降,且观察组均低于对照组(P<0.05)。观察组手足综合征、血小板减少、甲状腺功能减退、肾损伤、中性粒细胞减少Ⅰ/Ⅱ级、Ⅲ级发生率比较差异均无统计学意义(P>0.05)。观察组中位PFS(8.26个月比5.81个月)、中位OS(19.51个月比14.43个月)均更长(P<0.05)。结论 PD-1/PD-L1免疫抑制剂能够提高中晚期HCC患者的肿瘤治疗反应,降低总CTC数、总PD-L1⁺CTC数和血清VEGF、MMP-9水平,延长PFS和OS,且并未增加不良反应。

关键词: 循环肿瘤细胞, 程序性死亡受体1, 程序性死亡受体-配体1, 肝细胞癌

Abstract: Objective To investigate the efficacy of immunosuppressants programmed death-1/ programmed death ligand-1 (PD-1/PD-L1) in the treatment of hepatocellular carcinoma (HCC) based on TumorFisher circuiting tumor cells (CTCs) assay. Methods 120 patients with middle and advanced HCC treated in Yancheng People's Hospital of Jiangsu Province from August 2021 to December 2022 were selected and divided into two groups, with 60 cases in each group. The control group was treated with drug-eluting beads trans-arterial chemoembolization (DEB-TACE) combined with tyrosine kinase inhibitor (TKI), and the observation group was treated with PD-1/PD-L1 immunosuppressant. Tumor response, TumorFisher CTCs, serum vascular endothelial growth factor receptor (VEGFR), matrix metalloproteinase-9 (MMP-9) levels and adverse reactions were compared, and progression-free survival (PFS) and overall survival (OS) were followed-up. Results The objective response rate (ORR)(71.67% vs 53.33%) and disease control rate (DCR)(81.67% vs 63.33%) were higher in the observation group (P<0.05). After treatment, the total CTCs, total PD-L1⁺CTCs and serum VEGF and MMP-9 levels were decreased in both groups, and the levels were lower in the observation group (P<0.05). There was no significant difference in the incidence of hand-foot syndrome, thrombocytopenia, hypothyroidism, kidney injury and neutropenia grade I/II and grade III in the observation group (P>0.05). The median PFS (8.26 months vs 5.81 months) and the median OS (19.51 months vs 14.43 months) were longer in the observation group (P<0.05). Conclusion PD-1/PD-L1 immunosuppressive agents can improve tumor response in patients with middle and advanced HCC, decrease total CTCs number, total PD-L1⁺CTCs number, serum VEGF and MMP-9 levels, prolong PFS and OS, without increasing adverse reactions.

Key words: Circuiting tumor cells, Programmed death-1, Programmed death ligand-1, Hepatocellular carcinoma

徐静, 丁哲, 徐颖. 基于TumorFisher CTC检测探讨PD-1/PD-L1免疫抑制剂治疗肝细胞癌的效果[J]. 肝脏, 2024, 29(10): 1184-1188.

XU Jing, DING Zhe, XU Ying. The effect of PD-1/PD-L1 immunosuppressants on hepatocellular carcinoma based on TumorFisher CTCs[J]. Chinese Hepatolgy, 2024, 29(10): 1184-1188.

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