Multiplex immunohistochemistry to explore the tumor immune microenvironment in HCC patients with different GPC3 expression

作者：Mingzhen Zhou, Ziyan Zhou, Lina Hu, Sidong Chen, Fanyan Meng, Jun Chen, Jie Shen · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06106-0 · 被引用次数：6 · 研究领域：Cancer Immunotherapy and Biomarkers、Hepatocellular Carcinoma Treatment and Prognosis、Angiogenesis and VEGF in Cancer

GPC3 has been recognized as a promising target for immunotherapy in hepatocellular carcinoma (HCC). However, the GPC3-targeted immunotherapies have shown limited therapeutic efficacy. The use of anti-PD-1/PD-L1 monoclonal antibodies in HCC treatment is considerably constrained. Furthermore, there is still a notable lack of understanding concerning the immune landscape in HCC, especially regarding varied GPC3 expression levels. Therefore, thorough exploration of the intricate tumor immune microenvironment at different GPC3 expression levels is essential for guiding and improving HCC treatment strategies. Sixty patients with HCC were enrolled in this study, receiving a first-line treatment that combined anti-angiogenesis targeted drugs and immunotherapy. Immunohistochemistry was used to assess the levels of GPC3 expression. Multiple immunohistochemical markers, such as CD8, PD-1, LAG3, TIGIT, TIM-3, CD103, Claudin18.2, PD-L1, CD4, Foxp3, CD68, CD163, GPC3, CD11C, CD14, CD66b, and HLA-DR, were used to characterize the immune microenvironment and spatial distribution of immune cells in HCC tumors with different levels of GPC3 expression. Cell expression levels and spatial distribution were determined by fluorescence staining and subsequent analysis of fluorescence intensity using the Panoramic Pathology Workstation (Pano ATLAS). This approach facilitated a detailed examination of cell characteristics and spatial information within the samples. Based on the result of GPC3 immunohi...