The abstract is read at the publisher; the summary is JClub's.
Ursodeoxycholic acid enhances cancer radioimmunotherapy in peripheral blood mononuclear cell-humanized mice by suppressing a human-biased FXR–TRIM22–STAT1 immune brake.
- Why it matters: Radiotherapy can trigger type I interferon and innate immune pathways, but human tumors show attenuated DNA damage–driven immune activation versus mice, implying a human-specific checkpoint limiting radioimmunity.
- What they did: The study mapped a tumor-intrinsic FXR–TRIM22–STAT1 circuit where radiation stabilizes FXR via USP7, induces TRIM22, and TRIM22 promotes K48-linked STAT1 degradation to dampen cGAS–STING ISGs; ursodeoxycholic acid pharmacologically modulated this axis and was tested with radiotherapy ± anti-PD-1.
- The result: Disrupting FXR or TRIM22 preserved STAT1, amplified type I interferon signaling, and increased CD8a T-cell activation and abscopal control, while ursodeoxycholic acid suppressed radiation-induced TRIM22, restored STAT1–ISG signaling, potentiated radiotherapy alone or with anti-PD-1, and showed no overt toxicity in humanized models.
The findingWhy it mattersWhat they didThe result
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