Tissue-specific antitumor NK cell subsets identified in colorectal cancer liver metastases express candidate therapeutic targets.

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 checkpoin

SUBMITTER: Mikulak J 

PROVIDER: S-EPMC12704330 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature