Targeting the AHR-IDO1-kynurenine pathway in TREM2⁺ macrophages restores antitumor immunity in thyroid cancer.

Authors

Fei Le, Xianming Huang, Youfang Jiang, Saiping Lv, Yaoyao Chen

Published in

Frontiers in immunology. Volume 17. Pages 1826288. Epub Jul 21, 2026.

Abstract

Advances in single-cell technologies have provided detailed insight into cellular heterogeneity within tumor microenvironments. However, the regulatory mechanisms driving macrophage-mediated immune suppression in thyroid cancer remain incompletely understood.
We applied integrated single-cell multi-omics approaches to tumor samples from patients and murine thyroid cancer models, including single-cell RNA sequencing, single-cell ATAC sequencing, mass cytometry, spatial/histological validation, and in vitro and in vivo functional assays.
We identified a prominent enrichment of TREM2⁺ tumor-associated macrophages within the thyroid cancer immune microenvironment. These macrophages displayed an immunosuppressive transcriptional and metabolic profile and promoted immune evasion through activation of the AHR-IDO1-kynurenine signaling axis, leading to impaired CD8⁺ T-cell function. Pharmacological inhibition of AHR and IDO1 reversed immune suppression and reduced tumor burden in experimental models.
These findings reveal a TREM2⁺ macrophage-driven immunometabolic mechanism in thyroid cancer and suggest that targeting the AHR-IDO1-kynurenine pathway may provide a potential strategy for improving antitumor immunity.

PMID:
42553364
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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