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Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis

ABSTRACT: We report that a single dose of therapeutic Salmonella, a prominent anti-tumor bacterial therapy, provides long-lasting protection against metastasis in mice by inducing trained NK cells. Integrated functional and multi-omics analyses revealed that Salmonella-trained NK (stNK) cells establish an enduring reprogrammed epigenome characterized by enhanced pro-survival signaling and immune effector functions, resulting in more potent IFN-gamma release and cytotoxicity upon secondary stimulation. We further showed that this training requires a transient pulse of IL-12 combined with sustained IL-18 signaling. Crucially, stNK cells significantly outperform conventional immune checkpoint therapies, including PD-1 and TIGIT blockade, in preventing metastasis, underscoring the unique immunological mechanisms in combating metastasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE333350 | GEO | 2026/05/28

REPOSITORIES: GEO

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EZH2 identifies the precursors for trained immunity of human natural killer cells

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