Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medicine, National Yang-Ming University Hospital, I-Lan, Taiwan.
Int J Cancer. 2013 Dec 15;133(12):2895-902. doi: 10.1002/ijc.28311. Epub 2013 Jun 25.
Host immunity may have important role in the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the correlation between circulating immune regulators and clinical outcome in patients with HCC. Sixty-three HCC patients were prospectively enrolled. Serum levels of interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ) and interferon gamma-inducible protein 10 (IP-10) were measured, as well as the prevalence of regulatory T cells (Treg), NK(+) T cells, invariant natural killer T cells (iNKT), programmed cell death-1 (PD-1)(+) CD8(+) T cells, T helper 17 cells (Th17), CD69(+) and CD45RO(+) T cells in peripheral blood mononuclear cells (PBMC). Correlation between these immune regulators and clinical outcome were analyzed. A low serum IFN-γ level (<50 pg/mL) was significantly associated tumor stage (BCLC stage B: 61.25% vs. stage A: 25%, p = 0.010) and tumor size (>5 cm: 53.8% vs. <5 cm: 25%, p = 0.047). Recurrence-free survival was evaluated in 48 patients receiving curative treatment of HCC. By multivariate analysis, BCLC stage [hazard ratio (HR) = 32.180, p < 0.001], tumor size (HR = 15.373, p = 0.005), AST (HR = 3.796, p = 0.011) and IFN-γ (HR = 0.354, p = 0.018) levels were independent factors associated with recurrence-free survival. In conclusion, serum IFN-γ level correlates with tumor stage and tumor size in HCC patients. Patients with lower baseline IFN-γ levels have a higher risk of tumor recurrence after curative treatment. IFN-γ may reflect host anti-tumor immunity and may be a potential marker of HCC recurrence after curative treatment.
宿主免疫可能在肝细胞癌(HCC)的预后中起重要作用。本研究旨在评估循环免疫调节剂与 HCC 患者临床结局的相关性。前瞻性纳入 63 例 HCC 患者。检测血清白细胞介素-10(IL-10)、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)和干扰素γ诱导蛋白 10(IP-10)水平,以及外周血单个核细胞(PBMC)中调节性 T 细胞(Treg)、NK(+)T 细胞、固有自然杀伤 T 细胞(iNKT)、程序性细胞死亡-1(PD-1)(+)CD8(+)T 细胞、辅助性 T 细胞 17(Th17)、CD69(+)和 CD45RO(+)T 细胞的发生率。分析这些免疫调节剂与临床结局的相关性。低血清 IFN-γ水平(<50pg/mL)与肿瘤分期(BCLC 分期 B:61.25%比分期 A:25%,p=0.010)和肿瘤大小(>5cm:53.8%比<5cm:25%,p=0.047)显著相关。对 48 例接受 HCC 根治性治疗的患者进行无复发生存评估。多因素分析显示,BCLC 分期[风险比(HR)=32.180,p<0.001]、肿瘤大小(HR=15.373,p=0.005)、AST(HR=3.796,p=0.011)和 IFN-γ(HR=0.354,p=0.018)水平是与无复发生存相关的独立因素。总之,血清 IFN-γ水平与 HCC 患者的肿瘤分期和肿瘤大小相关。基线 IFN-γ水平较低的患者在根治性治疗后肿瘤复发的风险更高。IFN-γ可能反映宿主抗肿瘤免疫,可能是根治性治疗后 HCC 复发的潜在标志物。