Peritumoural adipose tissue promotes ferroptosis resistance by 3-hydroxykynurenine-mediated suppression of ferritinophagy
Zhang YY., Han Y., Tan YT., Lu YX., Ma MY., Zheng YQ.
Animal Study, published in Nat Cell Biol (2026) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Nat Cell Biol (2026)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41813885
- PMCID
- PMC13086588
- DOI
- 10.1038/s41556-026-01907-x
Abstract (original English)
The peritumoural adipose tissue (PAT) is a key contributor to cancer therapy resistance, yet its role in regulating ferroptosis remains unclear. Here we demonstrate that PAT confers ferroptosis resistance to cancer cells by upregulating ferritin (FTH1/FTL) and sequestering intracellular iron. PAT-derived kynurenine (KYN) was identified as the principal mediator. KYN is taken up by cancer cells and metabolized to 3-hydroxykynurenine, which directly binds to nuclear receptor coactivator 4 (NCOA4). This interaction inhibits NCOA4-mediated ferritinophagy, preventing ferritin degradation and limiting the free iron pool required for ferroptosis. In murine models, pharmacological inhibition of the KYN pathway synergized with PD-1 blockade to overcome ferroptosis resistance and suppress tumour progression. These findings reveal a PAT-KYN-ferritinophagy axis that promotes ferroptosis resistance, highlighting the potential of targeting adipose-tumour cross-talk to enhance immunotherapy in PAT-associated tumours.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
How we grade evidenceBrowse all related research
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