Ueshima Eisuke, Sofue Keitaro, Komatsu Shohei, Ishihara Nobuaki, Komatsu Masato, Umeno Akihiro, Nishiuchi Kentaro, Kozuki Ryohei, Yamaguchi Takeru, Matsuura Takanori, Tada Toshifumi, Murakami Takamichi
Department of Radiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.
Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.
Cancers (Basel). 2025 Mar 11;17(6):948. doi: 10.3390/cancers17060948.
: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). : We performed immunohistochemical staining with CD3 and CD8 antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). : HCCs with peritumoral enhancement in the arterial phase ( < 0.001) and rim APHE ( = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase ( = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature ( < 0.001). : We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.
虽然免疫疗法是中期肝细胞癌（HCC）的主要治疗选择，但其疗效各不相同。本研究旨在确定与动态对比增强计算机断层扫描（CECT）相关的、可预测免疫评分的非侵入性成像生物标志物。我们用CD3和CD8抗体进行免疫组织化学染色，并对侵袭边缘（IM）和肿瘤中心（CT）的阳性细胞进行计数，将其转化为0至4分的免疫评分。我们评估了96例行HCC肝切除术患者的动态CECT结果，并评估了动态CECT结果与免疫评分之间的关系。为进行验证，我们在另一组41例接受阿替利珠单抗和贝伐单抗联合免疫治疗（n = 27）以及度伐利尤单抗和曲美木单抗联合免疫治疗（n = 14）的患者中，使用实体瘤疗效评价标准评估了81个结节的治疗效果。在单变量线性回归分析中，动脉期瘤周强化（< 0.001）和边缘动脉期肝实质强化（APHE）（= 0.009）与免疫评分相关，在多变量线性回归分析中，动脉期瘤周强化（= 0.004）与免疫评分相关。动脉期有瘤周强化的HCC的结节进展时间明显长于无此特征的HCC（< 0.001）。我们将动脉期有瘤周强化的HCC确定为一种非侵入性成像生物标志物，以预测具有高免疫评分倾向的免疫炎症性HCC。这些HCC最有可能对联合免疫治疗产生反应。
