GPR183 senses 7α,25-OHC to drive T(reg) differentiation and tumor immune evasion via AXL-JAK2-STAT5 signaling.

7α,25-OHC sensed by GPR183 promotes Foxp3+ T reg differentiation and suppressive identity, linked to tumor immune evasion through AXL–JAK2–STAT5 signaling.

• Why it matters: Tumor T reg accumulation drives immune evasion and resistance to immunotherapy, yet the metabolic cues controlling T reg lineage commitment are not well defined.
• What they did: The study identifies 7α,25-OHC produced by Vimentin+ stromal cells as a GPR183 ligand, then tests cell-intrinsic roles using conditional GPR183 deletion in CD4+ T cells or T reg cells in syngeneic tumor models.
• The result: In gastric cancer, GPR183+ T reg infiltration correlates with advanced disease and poor survival; GPR183 loss abrogates immune evasion and restores CD8+ effector function, while GPR183 antagonism modestly enhances anti-PD-1 and blocks therapy-induced T reg expansion.

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