Our study reveals how transforming growth factor-β (TGFβ) enables liver metastasis of colorectal cancer (CRC) in two ways: by limiting CD8⁺ T cell recruitment and inducing SPP1⁺ macrophages. Inhibition of TGFβ sensitizes tumors to PD-L1 blockade therapy, eradicating metastases in different CRC genetic models. Targeting SPP1 offers therapeutic benefit while avoiding the systemic effects of complete TGFβ inhibition.
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References
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This is a summary of: Henriques, A. et al. TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages. Nat. Genet. https://doi.org/10.1038/s41588-025-02380-2 (2025).
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Two-pronged immunosuppression by TGFβ supports colorectal cancer metastasis. Nat Genet 57, 2956–2957 (2025). https://doi.org/10.1038/s41588-025-02379-9
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DOI: https://doi.org/10.1038/s41588-025-02379-9
