IFNAR1 stabilization sustains CD8(+) T cell persistence in IFN-high colorectal cancer liver metastases.

In IFN-I-high colorectal cancer liver metastases, effector CD8+ T cells show IFNAR1 loss, and reduced IFNAR1 expression stratifies patients with poor clinical outcomes.

• Why it matters: CRC liver metastases often resist immunotherapy, but the tumor-intrinsic immune-refractory mechanism—especially how chronic IFN signaling shapes effector T-cell behavior—remains unclear.
• What they did: The study combined patient-derived organoid transcriptional profiling with complementary preclinical models to link heterogeneous, recurrent tumor-derived IFN-I production to IFNAR1 internalization in IFN-I-high contexts.
• The result: Stabilizing IFNAR1 on the cell surface pharmacologically or genetically restored CD8+ T cell persistence, survival, and function, selectively enhancing TCR- and CAR-based immunotherapies in IFN-I-high tumors.

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