It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs havingCTNNB1mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase.
据报道,钆塞酸二钠增强磁共振成像(EOB-MRI)肝胆期(HB期)高信号与肝细胞癌(HCC)的免疫冷微环境相关。本研究旨在揭示非高信号HCC在免疫微环境方面是否具有同质性,并探讨EOB-MRI对阿特珠单抗联合贝伐珠单抗治疗(Atezo/Bev)反应的预测能力。研究首先在65例HCC患者(队列1)中,逐步分析了HB期信号强度差异与免疫微环境相关分子亚型及体细胞突变之间的关联。随后,在Atezo/Bev治疗队列(队列2,60例患者)中评估了EOB-MRI与Atezo/Bev治疗效果的关系。结果显示,HB期高信号组中CTNNB1突变、Chiang CTNNB1亚型及Hoshida S3亚型的HCC比例较高。肿瘤相关巨噬细胞(TAM)和调节性T淋巴细胞(Treg)的浸润分别是高信号组和低信号组的特征性表现。尽管EOB-MRI未能预测Atezo/Bev的治疗反应,但我们的结果表明,EOB-MRI可作为预测免疫微环境的替代标志物。这提示无论EOB-MRI肝胆期信号强度如何,均可选择Atezo/Bev治疗方案。