ArticleThe Journal of clinical investigation2025
Tissue-specific antitumor NK cell subsets identified in colorectal cancer liver metastases express candidate therapeutic targets.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- Single-cell analysis reveals corticosteroid-associated impairment of tumor-infiltrating NK cells in glioblastoma patients.Scientific reports · 2026Article
- Liver microenvironment-driven immunosuppressive niche in colorectal cancer liver metastasis and its therapeutic remodeling.Frontiers in immunology · 2026Review
- Disulfidptosis-related genes signature predicts prognosis and immune microenvironment in colon cancer.Frontiers in molecular biosciences · 2026Article
- The CXCL12-CXCR4 axis in colorectal cancer: immune regulation, metastatic progression, and therapeutic implications.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver metastases are relatively resistant to checkpoint blockade immunotherapy. The hepatic tissue has distinctive features including high numbers of NK cells. It was therefore important to conduct in-depth single-cell analysis of NK cells in colorectal cancer liver metastases (CRLMs) with an effort to dissect their diversity and to identify candidate therapeutic targets. By combining unbiased single-cell transcriptomic with multiparametric flow cytometry analysis, we identified an abundant family of intrahepatic CD56bright NK cells in CRLMs endowed with antitumor functions resulting from specific transcriptional liver programs. Intrahepatic CD56bright and CD56dim NK lymphocytes expressed unique transcription factors (IRF8, TOX2), a high level of chemokines, and targetable immune checkpoints, including CXCR4 and the IL-1 receptor family member IL-1R8. CXCR4 pharmacological blocking and an anti-IL-1R8 mAb enhanced the effector function of CRLM NK cells. Targeting the diversity of liver NK cells and their distinct immune checkpoint repertoires is key to optimize the current immune therapy protocols in CRLM.
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