ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- The natural killer-cellular humoral activation test as a functional biomarker of antibody-mediated rejection after kidney transplantation.Scientific reports · 2026Article
- Enhancing cancer killing and natural killer cell persistence by targeting NOXA, a predictor of poor patient survival.Molecular therapy. Oncology · 2026Article
- A Machine Learning Model Based on Clinical Factors to Predict the Efficacy of First-Line Immunochemotherapy for Patients With Advanced Gastric Cancer: Retrospective Study.JMIR medical informatics · 2025Article
- Recombinant antibodies from clonally expanded cancer-associated plasma cells.Cancer immunology, immunotherapy : CII · 2025Article
- A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells.Journal of experimental & clinical cancer research : CR · 2025Article
- HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Comprehensive single-cell and bulk transcriptomic analyses to develop an NK cell-derived gene signature for prognostic assessment and precision medicine in breast cancer.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.
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Registered trials
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