Immune index: A gene and cell prognostic signature for immunotherapy response prediction in hepatocellular carcinoma

The heterogeneity of tumor immune microenvironment (TIME) plays important roles in the development and immunotherapy response of hepatocellular carcinoma (HCC). Using machine learning algorithms, we introduced the immune index (IMI), a prognostic model based on the HCC immune landscape. We found tha...

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Published inPharmacological research Vol. 187; p. 106583
Main Authors Cui, Xiuliang, Han, Lu, Cui, Longjiu, Fu, Gongbo, Liu, Erdong, Wang, Duowei, Song, Bin, Zhang, Yongxiang, Zhou, Wenxia, Wang, Hongyang, Fu, Jing
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.01.2023
Subjects
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - genetics
CD8-Positive T-Lymphocytes
Hepatocellular carcinoma
Humans
Immune microenvironment
Immune therapy
Immunotherapy
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
Prognosis
Single cell
Tumor Microenvironment
Immune microenvironment
Prognosis
Immune therapy
Single cell
Hepatocellular carcinoma
HCC
ICB
TIME
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Summary:The heterogeneity of tumor immune microenvironment (TIME) plays important roles in the development and immunotherapy response of hepatocellular carcinoma (HCC). Using machine learning algorithms, we introduced the immune index (IMI), a prognostic model based on the HCC immune landscape. We found that IMI low HCCs were enriched in stem cell and proliferating signatures, and yielded more TP53 mutation and 17p loss compared with IMI high HCCs. More importantly, patients with high IMI exhibited better immune-checkpoint blockade (ICB) response. To facilitate clinical application, we employed machine learning algorithms to develop a gene model of the IMI (IMIG), which contained 10 genes. According to our HCC cohort examination and single-cell level analysis, we found that IMIG high HCCs exhibited favorable survival outcomes and high levels of NK and CD8+ T cells infiltration. Finally, after coculture with autologous tumor infiltrating lymphocytes, IMIG high tumor cells exhibited a better response to nivolumab treatment. Collectively, the IMI and IMIG may serve as powerful tools for the prognosis, classification and ICB treatment response prediction of HCC. [Display omitted]
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ISSN:1043-6618
1096-1186
1096-1186
DOI:10.1016/j.phrs.2022.106583