Molecular & cellular oncology · 2026
A positive feedback loop of kynurenine-AhR-EMT upregulates tryptophan metabolic enzymes via epigenetic modification to facilitate immune escape in triple-negative breast cancer.
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Jun Chen, Menghui Li, Ting Liu, Juan Chen
Аннотация
BACKGROUND: Triple-negative breast cancer (TNBC) is prone to immune escape, and the synergistic mechanism of kynurenine, AhR, and EMT remains unclear.
METHODS: TNBC cell lines and 4T1 orthotopic breast cancer mice were used for molecular, cellular, and in vivo intervention experiments.
RESULTS: Kynurenine induced EMT in an AhR-dependent way, promoted cell migration and invasion, upregulated CCL2/CCL22, and inhibited the function of CD8⁺GrB⁺ T cells. Snail overexpression promotes H3K4me3 histone modification at IDO1 and TDO2 promoters to epigenetically amplify tryptophan metabolic enzyme expression. The AhR antagonist CH-223191 blocked the loop and reversed tumor immune escape.
CONCLUSION: This study demonstrates that the kynurenine-AhR-EMT positive feedback loop drives immune escape in TNBC, providing a rationale for combined targeted therapy.
METHODS: TNBC cell lines and 4T1 orthotopic breast cancer mice were used for molecular, cellular, and in vivo intervention experiments.
RESULTS: Kynurenine induced EMT in an AhR-dependent way, promoted cell migration and invasion, upregulated CCL2/CCL22, and inhibited the function of CD8⁺GrB⁺ T cells. Snail overexpression promotes H3K4me3 histone modification at IDO1 and TDO2 promoters to epigenetically amplify tryptophan metabolic enzyme expression. The AhR antagonist CH-223191 blocked the loop and reversed tumor immune escape.
CONCLUSION: This study demonstrates that the kynurenine-AhR-EMT positive feedback loop drives immune escape in TNBC, providing a rationale for combined targeted therapy.