Comprehensive analysis of immune subtype characterization on identification of potential cells and drugs to predict response to immune checkpoint inhibitors for hepatocellular carcinoma  

作　　者：Guichuan Lai Biao Xie Cong Zhang Xiaoni Zhong Jielian Deng Kangjie Li Hui Liu Yuan Zhang Anbin Liu Yi Liu Jie Fan Tianyi Zhou Wei Wang Ailong Huang 

机构地区：[1]Department of Health Statistics,School of Public Health,Chongqing Medical University,Chongqing 401331,China [2]Department of Applied Statistics,School of Public Health,Chongqing Medical University,Chongqing 401331,China [3]Department of Epidemiology,School of Public Health,Chongqing Medical University,Chongqing 401331,China [4]Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education),Institute for Viral Hepatitis,Department of Infectious Diseases,The Second Affiliated Hospital,Chongqing Medical University,Chongqing 400010,China

出　　处：《Genes & Diseases》2025年第3期463-477,共15页基因与疾病(英文)

基　　金：supported by the Science and Technology Research Programme Project of Chongqing Municipal Education Commission of China(No.KJQN202300423);the National Youth Science Foundation Project(China)(No.82204159);the Science and Technology Project of Sichuan Provincial Administration of Traditional Chinese Medicine(China)(No.2023MS047);the Program for Youth Innovation in Future Medicine,Chongqing Medical University(No.W0150);the Intelligent Medicine Research Project of Chongqing Medical University(No.ZHYX202223).

摘　　要：Immunosubtyping enables the segregation of immune responders from non-responders. However, numerous studies failed to focus on the integration of cellular heterogeneity and immunophenotyping in the prediction of hepatocellular carcinoma (HCC) patients’response to immune checkpoint inhibitors (ICIs). We categorized HCC patients into various immune subtypes based on feature scores linked to ICI response. Single-cell sequencing technology was to investigate the cellular heterogeneity of different immune subtypes and acquiresignificant ICI response-associated cells. Candidate drugs were identified using a blend ofvarious drug databases and network approaches. HCC patients were divided into two distinct immune subtypes based on characterization scores of 151 immune-related gene sets. Patientsin both subtypes showed varying overall survival, immunity levels, biological activities, andTP53 mutation rates. Subtype 1-related natural killer cells showed a positive correlation withimmune-promoting scores but a negative correlation with immune-suppressing scores.Notably, docetaxel sensitivity in HCC patients rose as the levels of subtype 1-related naturalkiller cells increased. Our study demonstrated that immune subtypes have cellular heterogeneity in predicting response to ICIs. A combination of subtype 1-associated natural killer cellsand docetaxel may offer new hope for ICI treatment in HCC.

关 键 词：Cellular heterogeneity Drug prediction Hepatocellular carcinoma Immune checkpoint inhibitors Immunosubtyping 

分 类 号：R735.7[医药卫生—肿瘤]