To elucidate the molecular mechanism by which TREM2+ macrophages drive immune tolerance in thyroid cancer through the AHR-IDO1-Kyn signaling axis.
Approach:
Single-cell multi-omics: Utilized integrated single-cell RNA sequencing, single-cell ATAC sequencing, mass cytometry, and functional assays on tumor samples from patients and murine thyroid cancer models.
Key Findings:
TREM2+ tumor-associated macrophages were enriched in the thyroid cancer immune microenvironment.
These macrophages exhibited an immunosuppressive profile and activated the AHR–IDO1–kynurenine signaling axis, impairing CD8+ T-cell function.
Pharmacological inhibition of AHR and IDO1 reversed immune suppression and reduced tumor burden in experimental models.
Interpretation:
The study reveals a TREM2+ macrophage-driven immunometabolic mechanism in thyroid cancer.
Limitations:
The metabolic context of TREM2+ macrophages may vary across different tumor microenvironments.
The study primarily focuses on murine models, which may not fully replicate human thyroid cancer biology.
Conclusion:
Targeting TREM2+ macrophages and the AHR–IDO1–kynurenine pathway could represent a strategy for improving immune responses in thyroid cancer.
