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 hepat...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.展开更多
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)+2 种基金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).
文摘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.
