Evasion of Hepatic ILC1 Immunosurveillance Drives Breast Cancer Liver Metastasis

Liver-resident ILC1 immunosurveillance is linked to delayed breast cancer liver metastasis and better survival, and it is bypassed by DR5 loss and host metabolic dysfunction.

• Why it matters: Organ-specific immune barriers that limit metastasis are not well defined, limiting anti-metastatic therapy design.
• What they did: In a multi-organ metastatic breast cancer patient cohort, liver metastasis timing and survival were compared across organs, and elevated body mass index was assessed as a risk factor; mice were then fed a high-fat diet to induce hepatosteatosis and test colonization.
• The result: ILC1s restrained liver colonization, and clearance required cancer-cell DR5 with AP-2a (TFAP2A)–driven activation; TNFRSF10B deletion reduced DR5 and hepatosteatosis lowered macrophage IL-15, depleting ILC1s, reversible with GLP-1 receptor agonists.

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