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Published in: Breast Cancer 1/2024

Open Access 19-11-2023 | Breast Cancer | Original Article

IDO-1 impairs antitumor immunity of natural killer cells in triple-negative breast cancer via up-regulation of HLA-G

Authors: Rui Jing, Shukun Bai, Peipei Zhang, Hao Ren, Lintao Jia, Weimiao Li, Guoxu Zheng

Published in: Breast Cancer | Issue 1/2024

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Abstract

Background

Triple-negative breast cancers (TNBC) are highly aggressive malignancies with poor prognosis. As an essential enzyme in the tryptophan–kynurenine metabolic pathway, indoleamine 2,3 dioxygenase-1 (IDO-1) has been reported to facilitate immune escape of various tumors. However, the mechanism underlying the immunosuppressive role of IDO-1 in TNBC remains largely uncharacterized.

Methods

We examined the IDO-1 expression in 93 clinical TNBC tissues and paired adjacent normal tissues, and analyzed the regulation role of environmental cytokines like IFN-γ in IDO-1 expression. The effect of IDO-1 expression in TNBC cells on the function of NK cells were then evaluated and the underlying mechanisms were exploited.

Results

IDO-1 expressed in 50 of 93 (54.1%) TNBC patients. TNBC patients with high IDO-1 expression tended to have more infiltrated immune cells including NK cells, which are less active than patients with low IDO-1 expression. NK cells could produce IFN-γ, which induced IDO-1 expression in TNBC cells, whereas IDO-1 impaired the cytotoxicity of co-cultured NK cells by upregulation of HLA-G. Blockade of HLA-G improved the antitumor activity of NK cells to TNBC in vivo.

Conclusion

TNBC cells induce dysfunction of NK cells through an IFN-γ/IDO-1/HLA-G pathway, which provide novel insights into the mechanisms of TNBC progression and demonstrate the applicability of IDO-1 and HLA-G targeting in the treatment of TNBC.
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Metadata
Title
IDO-1 impairs antitumor immunity of natural killer cells in triple-negative breast cancer via up-regulation of HLA-G
Authors
Rui Jing
Shukun Bai
Peipei Zhang
Hao Ren
Lintao Jia
Weimiao Li
Guoxu Zheng
Publication date
19-11-2023
Publisher
Springer Nature Singapore
Published in
Breast Cancer / Issue 1/2024
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-023-01522-w

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