Research ArticleCANCER IMMUNOLOGY

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis

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Science Immunology  02 Oct 2020:
Vol. 5, Issue 52, eaba0759
DOI: 10.1126/sciimmunol.aba0759

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Salvage immunotherapy after liver metastases

Checkpoint blockade immunotherapy with anti–PD-1 is less effective in patients with cancer who have tumors that have metastasized to the liver. To unravel the mechanistic basis of suppressed antitumor immunity in this patient group, Lee et al. developed a preclinical mouse model in which liver tumors led to antigen-specific suppression of systemic immunity to extrahepatic tumors. Suppressed tumor immunity was associated with CTLA-4hi Tregs responsible for inducing myeloid-derived suppressor cells. Depletion of tumor-resident Tregs by anti–CTLA-4 treatment or functional inactivation of Tregs by treatment with an EZH2 inhibitor rescued the therapeutic potential of PD-1 blockade. The findings from the mouse model provide a basis for pursuing translational studies of salvage immunotherapy approaches that combine anti–PD-1 with Treg-targeting agents in patients with cancer and hepatic metastases.

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