Wang Zhu-Tao, Guan Ruo-Yu, Gan Wei, Yang Zhang-Fu, Sun Bao-Ye, Wu Jing-Fang, Zhang Dai, Sun Guo-Qiang, Gao Xu-Kang, Huang Jin-Long, Liu Gao, Zhou Cheng, Zhou Jian, Fan Jia, Yi Yong, Hu Bo, Qiu Shuang-Jian
Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Med. 2024 Dec;13(23):e70459. doi: 10.1002/cam4.70459.
The immune microenvironment (IME) plays a crucial role in the progression of hepatocellular carcinoma (HCC). In HCC, the IME is often compromised by hepatitis B virus (HBV) infection, chronic inflammation, and fibrosis. Both antiviral therapy (AVT) and the alleviation of inflammation and fibrosis (AIF) have been shown to improve prognosis. However, the relationship among the IME of HCC, AVT, and AIF remains unclear.
A total of 140 and 110 primary HBV-related HCC patients were enrolled as training and validation sets, respectively, to establish a HCC-immune microenvironment score (H-IME score). Immunohistochemistry was performed to assess the number of granzyme B+ (GrB+) and Foxp3+ cells, as well as the expression of CTLA-4, PD-1, LAG3, TIGIT, TIM3, and VISTA. Another cohort consisting of 114 recurrent HBV-related HCC patients with paired primary and recurrent tissues was used to study the relationship among the IME of HCC, AVT, and AIF.
The H-IME score, including GrB, Foxp3, CTLA-4, PD-1, LAG3, and TIGIT, was established to evaluate the IME. A higher H-IME score indicates stronger immunosuppressive activities. Both AVT and AIF were found to inhibit immunosuppressive activities in the IME. Compared to primary tumors, the H-IME scores of recurrent tumors in the effective AVT group (e-AVT, classified by HBV DNA) with AIF decreased, while the scores increased in the non-AVT group without AIF.
The IME of HCC is closely related to AVT and AIF. e-AVT can enhance anti-tumor activities in the IME by alleviating inflammation and fibrosis.
免疫微环境（IME）在肝细胞癌（HCC）进展中起关键作用。在HCC中，IME常因乙型肝炎病毒（HBV）感染、慢性炎症和纤维化而受损。抗病毒治疗（AVT）以及炎症和纤维化的缓解（AIF）均已显示可改善预后。然而，HCC的IME、AVT和AIF之间的关系仍不清楚。
分别纳入140例和110例原发性HBV相关HCC患者作为训练集和验证集，以建立HCC免疫微环境评分（H-IME评分）。采用免疫组织化学法评估颗粒酶B+（GrB+）和Foxp3+细胞数量以及CTLA-4、PD-1、LAG3、TIGIT、TIM3和VISTA的表达。另一组由114例复发性HBV相关HCC患者组成，其具有配对的原发和复发组织，用于研究HCC的IME、AVT和AIF之间的关系。
建立了包括GrB、Foxp3、CTLA-4、PD-1、LAG3和TIGIT的H-IME评分来评估IME。较高的H-IME评分表明免疫抑制活性更强。发现AVT和AIF均能抑制IME中的免疫抑制活性。与原发性肿瘤相比，有效AVT组（根据HBV DNA分类为e-AVT）伴有AIF的复发性肿瘤的H-IME评分降低，而无AIF的非AVT组评分升高。
HCC的IME与AVT和AIF密切相关。e-AVT可通过减轻炎症和纤维化增强IME中的抗肿瘤活性。
