Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype - Takeaways - MDSpire
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Identification of Aggressive Acral Melanoma Phenotype with Depleted NK Cells and Resistance to Checkpoint Inhibition through Locus-Specific HERV Expression

  • By

  • Jez L. Marston

  • Tongyi Fei

  • Helena Reyes-Gopar

  • Matthew L. Bendall

  • Douglas F. Nixon

  • July 6, 2026

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  • 1

    Acral melanoma (AM) is a non-UV-derived melanoma subtype with worse survival outcomes compared to UV-driven melanomas.

  • 2

    A three-locus HERV signature stratifies AM tumors by overall survival, demonstrating strong prognostic value.

  • 3

    High-risk AM tumors exhibit depletion of natural killer (NK) cells and show reduced response to immune checkpoint inhibitors.

  • 4

    The study identifies a structurally intact HERV-K antigen candidate that may serve as a target for immunotherapy.

  • 5

    Locus-specific dysregulation of transposable elements, particularly HERVs, may contribute to AM's aggressive behavior and immunosuppressive state.

Original Source(s)

Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype

  • by Jez L. Marston, Tongyi Fei, Helena Reyes-Gopar, Matthew L. Bendall, Douglas F. Nixon

  • July 6, 2026

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