ArticleProceedings of the National Academy of Sciences of the United States of America2025
Cancer cells suppress NK cell activity by actin-driven polarization of inhibitory ligands to the immunological synapse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- LIM and SH3 protein 1 deficiency confers resistance to cytotoxic lymphocyte-mediated lysis and immunotherapy in gastric cancer by disrupting cytoskeleton dynamics.Journal for immunotherapy of cancer · 2026Article
- Deep learning-enabled single-cell morpholomic atlas of nasal swabs distinguishes chronic inflammation from sinonasal malignancy.NPJ precision oncology · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
Natural killer (NK) cells engage target cells via the immunological synapse (IS), where inhibitory and activating signals determine whether NK cell cytotoxicity is suppressed or activated. We previously reported that cancer cells can rapidly remodel their actin cytoskeleton upon NK cell engagement, leading to F-actin accumulation at the synapse. Here, we show that this process inhibits NK cell activation as indicated by impaired MTOC and lytic granule polarization. Exploring the underlying mechanism, we demonstrate that actin remodeling drives the recruitment of inhibitory ligands, such as HLA-A, -B, and -C, to the synapse. Disrupting HLA interaction with their cognate inhibitory receptors KIRs restores NK cell activation. Using NK cells expressing inhibitory KIR receptors, matched or unmatched to HLA molecules on cancer cells, we show that synaptic F-actin accumulation and matching KIR-HLA interactions jointly suppress NK cell cytotoxicity. Our findings reveal an immune evasion strategy in which cancer cells impair NK cell activation by altering synaptic signaling through actin cytoskeleton-driven recruitment of inhibitory signals to the IS.
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