Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

IF 5.5 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Gastroenterology Pub Date : 2025-03-01 Epub Date: 2024-12-09 DOI:10.1007/s00535-024-02185-w

Ryoichi Miura, Atsushi Ono, Hikaru Nakahara, Yuki Shirane, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Takeshi Kishi, Waka Ohishi, Naoya Sakamoto, Koji Arihiro, Clair Nelson Hayes, Shiro Oka

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Abstract

Background: This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC).

Methods: 96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens.

Results: In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = -0.4, p < 0.01).

Conclusion: Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

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血清IL-6浓度是预测阿特唑单抗联合贝伐单抗治疗肝癌患者疗效的有用生物标志物。

背景：本研究旨在确定atezolizumab联合贝伐单抗（Atezo+Bev）治疗肝细胞癌（HCC）患者治疗反应的生物标志物。方法：96例接受Atezo+Bev或lenvatinib作为一线全身治疗的患者，经倾向评分匹配（PSM）后作为训练组，42例接受Atezo+Bev治疗的患者作为验证组。治疗开始时采用Luminex multiplex法测定17种血清细胞因子。为了进一步评估细胞因子水平与肿瘤微环境（TME）之间的关系，对治疗前肝活检标本进行免疫组化（IHC）。结果：在衍生集中，多因素分析发现IL-6升高是Atezo+Bev组的独立危险因素（HR 5.80: p）。结论：血清IL-6水平被认为参与抑制肿瘤免疫，并有助于预测Atezo+Bev治疗的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.