Zhang Yumo, He Jitian, Li Xue, Han Zhibo, Chen Huaiyong, Yang Zhouxin, Wang Youwei
Institute of Medical Engineering & Translational Medicine, Tianjin University, Tianjin, 300072, China.
Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510275, China.
Immunol Res. 2025 Aug 23;73(1):122. doi: 10.1007/s12026-025-09665-y.
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.
单细胞转录组分析在新细胞谱系的鉴定和癌症免疫微环境的研究方面做出了杰出贡献。然而，人类肝脏1型天然淋巴细胞（ILC1s）的特征及其在肿瘤微环境中的动态变化尚未在如此详细的层面上得到充分研究。在此，我们对小鼠和人类肝脏免疫细胞进行了综合分析，以基于已鉴定的小鼠肝脏ILC1s来鉴定人类肝脏ILC1s，并验证其功能相似性。此外，我们的研究结果突出了转录因子EOMES在人类与小鼠肝脏ILC1s中的不同表达模式，表明与小鼠模型相比，其在人类肝脏自然杀伤（NK）细胞和ILC1s中的调节意义降低。我们鉴定出了一个独特的中间天然淋巴细胞（intILCs）亚群，其兼具人类肝脏NK细胞和ILC1s的特征。利用单细胞RNA测序（scRNA-seq）数据分析和TCGA数据集来表征人类肝细胞癌（HCC）中NK细胞、ILC1s和intILCs在基因和功能上的明显改变。研究发现，肝脏ILC1s和intILCs及其一些亚群的动态变化可能是肿瘤进展的关键因素。本研究为人类肝脏中ILC1s的鉴定以及肿瘤微环境中天然淋巴细胞（ILCs）的免疫变化和机制提供了新的见解，这些发现可能适用于改善肝细胞癌的诊断和治疗。
