Natural Killer Cell Activation Signature Identifies Cyclin B1/CDK1 as a Druggable Target to Overcome Natural Killer Cell Dysfunction and Tumor Invasiveness in Melanoma.

ABSTRACT: Background/Objectives: Natural killer (NK) cells play a crucial role in immune surveillance against melanoma, yet they frequently exhibit dysfunction in the tumor microenvironment. This study aims to establish an NK cell activation-related prognostic signature and identify potential druggable targets to overcome NK cell dysfunction. Methods: A prognostic signature was developed using the TCGA-SKCM cohort and validated across independent datasets. NK cell activation and cytotoxicity were evaluated in melanoma-NK-92MI co-culture systems via flow cytometry. Mechanistic studies employed Western blotting, co-immunoprecipitation, ELISA, and qRT-PCR. Single-cell RNA-seq data were used to analyze cell-cell communication. Results: A four-gene NK cell activation signature was id

SUBMITTER: Chen L 

PROVIDER: S-EPMC12114673 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature