A positive feedback loop of kynurenine-AhR-EMT upregulates tryptophan metabolic enzymes via epigenetic modification to facilitate immune escape in triple-negative breast cancer
Year: 2026
Type: article
Abstract: 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.
Source: Molecular & Cellular Oncology
Authors: Chen Jun, Li Menghui, Liu Ting, Chen Juan
Institution: Third Hospital of Nanchang
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,590
OpenAlex ID: W7221751564