Dissecting the heterogeneity and tumor-associated dynamics of human liver group I ILC via scRNA sequencing data

Single-cell transcriptome analysis has made outstanding contributions to the identification of new cell lineages and the study of cancer immune microenvironment. Yet, the characterization of human liver type 1 innate lymphoid cells (ILC1s) and their dynamic changes in the tumor microenvironment have not been thoroughly studied at this detailed level. Here, we performed an integrated analysis of mouse and human liver immune cells to identify human liver ILC1s based on identified mouse liver ILC1s and to verify its functional similarity. Additionally, our findings highlighted the different expression patterns of the transcription factor EOMES in human versus mouse liver ILC1s, suggesting its reduced regulatory significance in human liver nature killer (NK) cells and ILC1s compared to murine models. A unique subset of intermediate innate lymphoid cells (intILCs) was identified, exhibiting traits of both human liver NK cells and ILC1s. Single-cell RNA sequencing (scRNA-seq) data analysis and TCGA dataset were utilized to characterize the distinct alterations in the genes and functions of NK cells, ILC1s, and intILCs in human hepatocellular carcinoma (HCC). It was found that the dynamic changes of liver ILC1s and intILCs, along with some of their subpopulations, may be key factors in tumor progression. This study provided new insights into the identification of ILC1s in human liver and the immunologic changes and mechanism of innate lymphoid cells (ILCs) in the tumor microenvironment, and these findings may be applicable to improving the diagnosis and treatment of hepatocellular carcinoma.