Department of Hepatic Surgery (V), The Third Affiliated Hospital of Naval Medical University, Shanghai, China.
The Medical Department, 3D Medicines Inc., Shanghai, China.
Front Immunol. 2023 Mar 28;14:1116057. doi: 10.3389/fimmu.2023.1116057. eCollection 2023.
BACKGROUND & AIMS: Little is known about molecular biomarkers that predict the response and prognosis in unresectable hepatocellular carcinoma (HCC) treated with programmed death (PD)-1 inhibitors.
A total of 62 HCC patients who underwent next-generation sequencing were retrospectively included in our department for this study. Patients with unresectable disease were subjected to systemic therapy. PD-1 inhibitors intervention (PD-1Ab) group and nonPD-1Ab group included 20 and 13 patients, respectively. Primary resistance was defined as initial on-treatment progression or progression with an initial stable disease of less than 6 months.
Chromosome 11q13 amplification (Amp11q13) was the most common copy number variation in our cohort. Fifteen (24.2%) patients harbored Amp11q13 in our dataset. Patients with Amp11q13 showed higher level of Des-γ-carboxy-prothrombin (DCP), tumor number and were more prone to be combined with portal vein tumor thrombosis (PVTT). In the PD-1Ab group, the proportion of progressive disease (PD) in patients with Amp11q13 was significantly higher than that in patients with nonAmp11q13 (100% vs 33.3%, =0.03). In the nonPD-1Ab group, the proportion of PD in patients with Amp11q13 and nonAmp11q13 had no significant difference (0% vs 11.1%, >0.99). In the PD-1Ab group, the median progression-free survival (PFS) was 1.5 months in Amp11q13 patients vs 16.2 months in non-Amp11q13 patients (HR, 0.05; 95% CI 0.01-0.45; = 0.0003). No significant difference was observed in the nonPD-1Ab group. Notably, we found that hyperprogressive disease (HPD) might be associated with Amp11q13. The increased density of Foxp3+ Treg cells in HCC patients with Amp11q13 might be one of potential mechanisms.
HCC patients with Amp11q13 are less likely to benefit from PD-1 blockade therapies. These findings may help guide the use of immunotherapy for HCC in routine clinical practice.
关于预测不可切除肝细胞癌（HCC）患者对程序性死亡（PD）-1 抑制剂反应和预后的分子生物标志物知之甚少。
本研究回顾性纳入了在我院接受下一代测序的 62 例 HCC 患者。对不可切除疾病患者进行系统治疗。PD-1 抑制剂干预（PD-1Ab）组和非 PD-1Ab 组分别包括 20 例和 13 例患者。原发性耐药定义为初始治疗进展或初始稳定疾病进展时间少于 6 个月。
在我们的队列中，11q13 染色体扩增（Amp11q13）是最常见的拷贝数变异。在我们的数据集中，有 15 例（24.2%）患者存在 Amp11q13。携带 Amp11q13 的患者 DCP 水平更高，肿瘤数量更多，更易合并门静脉癌栓（PVTT）。在 PD-1Ab 组中，携带 Amp11q13 的患者进展性疾病（PD）的比例明显高于未携带 Amp11q13 的患者（100% vs. 33.3%，=0.03）。在非 PD-1Ab 组中，携带 Amp11q13 和未携带 Amp11q13 的患者 PD 比例无显著差异（0% vs. 11.1%，>0.99）。在 PD-1Ab 组中，携带 Amp11q13 的患者中位无进展生存期（PFS）为 1.5 个月，未携带 Amp11q13 的患者为 16.2 个月（HR，0.05；95%CI，0.01-0.45；=0.0003）。在非 PD-1Ab 组中未观察到差异。值得注意的是，我们发现超进展性疾病（HPD）可能与 Amp11q13 相关。携带 Amp11q13 的 HCC 患者中 Foxp3+Treg 细胞的密度增加可能是潜在的机制之一。
携带 Amp11q13 的 HCC 患者不太可能从 PD-1 阻断治疗中获益。这些发现可能有助于指导 HCC 患者免疫治疗在常规临床实践中的应用。
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