Mukozu Takanori, Nagai Hidenari, Nagumo Hideki, Mohri Kunihide, Yoshimine Naoyuki, Kobayashi Kojiro, Ogino Yu, Matsui Teppei, Daido Yasuko, Wakui Noritaka, Momiyama Koichi, Higai Koji, Matsuda Takahisa, Igarashi Yoshinori
Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan.
Department of Medical Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
Oncology. 2025;103(4):277-289. doi: 10.1159/000541372. Epub 2024 Sep 12.
In atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously, we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial basis. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC.
The study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment.
Significant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second-line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period.
In patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.
在阿替利珠单抗联合贝伐单抗（阿替利珠单抗/贝伐单抗）的联合治疗中，两种药物均作用于免疫系统。此前，我们报道了阿替利珠单抗/贝伐单抗用于不可切除肝细胞癌（uHCC）治疗后免疫变化情况，显示白细胞介素（IL）-6、可溶性IL-2受体、肿瘤坏死因子-α和程序性细胞死亡蛋白1水平有显著改变。在这些可变因素中，血清IL-6水平可通过商业途径轻松检测。因此，本研究旨在探讨血清IL-6作为uHCC患者对阿替利珠单抗/贝伐单抗治疗肿瘤反应预测指标的效用。
本研究纳入44例接受阿替利珠单抗/贝伐单抗治疗的HCC患者。在治疗前和治疗后3周采集血样，并在治疗后6周使用对比增强计算机断层扫描评估肿瘤反应。
在接受阿替利珠单抗/贝伐单抗一线治疗的患者中观察到血清IL-6水平有显著变化，而在接受二线或更晚期治疗的患者中未观察到。在接受阿替利珠单抗/贝伐单抗一线治疗的患者中，完全或部分缓解的患者治疗后血清IL-6水平显著升高，而病情稳定或进展的患者则未升高。此外，与其他肿瘤标志物如甲胎蛋白、甲胎蛋白的豆凝集素反应性部分和异常凝血酶原相比，血清IL-6水平在预测治疗期间肿瘤反应方面表现出最高的敏感性。
在接受阿替利珠单抗/贝伐单抗治疗的uHCC患者中，血清IL-6水平可作为肿瘤反应的潜在预测指标。治疗后水平升高可能表明肿瘤反应良好及预后较好。
