Zhang Dongjing, Lu Bingyun, Ma Qianqian, Xu Wen, Zhang Qi, Xiao Zhiqi, Li Yuanheng, Chen Ren, Wang An-Jiang
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Department of Infectious Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Heliyon. 2025 Jan 7;11(2):e41380. doi: 10.1016/j.heliyon.2024.e41380. eCollection 2025 Jan 30.
Accumulating studies have highlighted the biological significance of immunogenic cell death (ICD) in cancer immunity. However, the influence of ICD on tumor microenvironment (TME) formation and immune response in Hepatocellular carcinoma (HCC) remains largely unexplored. In this study, we systematically analyzed the mRNA profiles of ICD-related genes in 1847 HCC patients and identified three molecular subtypes with significantly different immune features and prognostic stratification. A reliable risk model named ICD score was constructed via machine learning algorithms to assess the immunological status, therapeutic responses, and clinical outcomes of individual HCC patients. High ICD score indicated an immune-excluded TME phenotype, with lower anticancer immunity and shorter survival time. In contrast, low ICD score corresponded to abundant immune cell infiltration, high sensitivity to immunotherapy and a positive prognosis, indicating an "immune-hot" phenotype. Pan-cancer analysis further validated a negative association between ICD score and the immune cell infiltration levels. In conclusion, our findings revealed that the ICD score could serve as a robust prognostic biomarker to predict the benefits of immunotherapy and optimize the clinical decision-making of HCC patients.
越来越多的研究凸显了免疫原性细胞死亡(ICD)在癌症免疫中的生物学意义。然而,ICD对肝细胞癌(HCC)肿瘤微环境(TME)形成和免疫反应的影响在很大程度上仍未得到探索。在本研究中,我们系统分析了1847例HCC患者中ICD相关基因的mRNA谱,并确定了三种具有显著不同免疫特征和预后分层的分子亚型。通过机器学习算法构建了一个名为ICD评分的可靠风险模型,以评估个体HCC患者的免疫状态、治疗反应和临床结局。高ICD评分表明存在免疫排除性TME表型,抗癌免疫力较低,生存时间较短。相反,低ICD评分对应着丰富的免疫细胞浸润、对免疫治疗的高敏感性和良好的预后,表明是一种“免疫激活”表型。泛癌分析进一步验证了ICD评分与免疫细胞浸润水平之间的负相关。总之,我们的研究结果表明,ICD评分可作为一个强大的预后生物标志物,用于预测免疫治疗的益处并优化HCC患者的临床决策。
Int J Nanomedicine. 2024
Int J Pharm. 2024-5-10