Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing

Abstract

Objective: NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells. However, the developmental progression, transcriptomic landscape, and functional subtypes of liver NK cells are not well defined. Hepatocellular carcinoma (HCC) accounts for approximately 80% of primary liver cancer worldwide, yet the biological characteristics of NK cells in the HCC environment are unclear. Therefore, we aimed to determine these cells’ roles in tumorigenesis and prognosis. Methods: We compared the single-cell RNA sequencing profiles of NK cells purified from blood (n = 1), healthy liver tissues (n = 3), HCC tumor tissues (n = 4), and peritumor liver tissues (n = 1) to identify NK cell subsets. Furthermore, we performed bioinformatics analysis by using The Cancer Genome Atlas (TCGA) data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC. Results: Transcriptomic analysis revealed 5 NK cell subsets (L1-NK-CD56bright, L2-NK-CD56dim, L3-NK-HLA, L4-LrNK-FCGR3A, and L5-LrNK-XCL1) in the healthy liver tissues. However, the transitional L3 subset and the CXCR6+CD16+ L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues. Furthermore, 4 common prognosis-associated genes (RHOB, TALDO1, HLA-DPA1, and TKT) were significantly overexpressed in the paired tumor tissue and blood. Conclusions: Our study revealed 5 specific subsets of NK cells in healthy human liver tissues. However, only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues. The cytotoxic NK cell subsets were absent in HCC tissues. Furthermore, we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma

“…The changes of infiltrated immune cells may be related to the immunosuppressive microenvironment in HCC and correlated with HCC progression ( 62 ). Previous studies mostly conducted scRNA-seq analysis on HCC tumor tissues and focused on the heterogeneity of tumor microenvironment, while few studies on scRNA-seq of HCC peripheral blood single cells ( 63 ). The scRNA-seq analysis of peripheral blood immune cells combined with the immune characteristics of tumor microenvironment would be more beneficial to explore the mechanism of development and the treatment strategy of HCC.…”

Aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for acute myeloid leukemia: a comprehensive single-cell RNA sequencing analysis

“…The aggrephagy-mediated cell clusters were identified based on differentially expressed genes (DEGs) with log Fold Change (logFC) and aggrephagy-related genes. The NK cell subtypes were summarized from the published literature of Huan Liu et al ( 37 ).…”

Combining bulk and single-cell RNA-sequencing data to develop an NK cell-related prognostic signature for hepatocellular carcinoma based on an integrated machine learning framework

“…GSE14520 data set ( n = 242) and GSE76427 data set ( n = 115) from Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ), and ICGC–LIRI–JP data set ( n = 260) from International Cancer Genome Consortium (ICGC) database ( https://dcc.icgc.org/ ) were utilized to verify the predictive power of the prognostic model. The single-cell RNA-seq data were obtained from 3 HCC samples (GSM4955419, GSM4955421, and GSM4955426) in GSE162616 data set from GEO database [ 33 ]. Moreover, the two immunotherapy cohorts, GSE91061 and PRJEB23709 data set from GEO database, were also used to externally validate the predictive power of ICI response of the model.…”