Nuclear PD-L1 drives IFN-γ-promoted lung metastasis of triple-negative breast cancer via POLR2A-mediated transcriptional activation of LY6E
Our findings unveil a novel IFN-γ-nuclear PD-L1/POLR2A-LY6E signaling axis critical for TNBC lung metastasis. This immune-independent mechanism, driven by nuclear PD-L1 transcriptional activity, provides a mechanistic basis for the limited efficacy of anti-PD-L1 antibodies against metastasis and nominates nuclear PD-L1 complexes and LY6E as potential therapeutic targets to overcome metastatic resistance in TNBC.
Authors
- Ming Shi (ORCID: https://orcid.org/0000-0001-9263-6468)
- Zhangchun Guan
- Rui Hou
- Xu Wei (ORCID: https://orcid.org/0000-0001-6723-9604)
- Dan Liu (ORCID: https://orcid.org/0000-0002-2198-3910)
- Pu Wang (ORCID: https://orcid.org/0000-0002-9185-1913)
- Xu Wang (ORCID: https://orcid.org/0000-0001-6301-3587)
- Xuan Zhao (ORCID: https://orcid.org/0000-0001-9219-820X)
- Sijin Li (ORCID: https://orcid.org/0000-0002-5867-8362)
- Qi Zhou (ORCID: https://orcid.org/0000-0002-0441-584X)
- Wen Ma (ORCID: https://orcid.org/0009-0004-9510-7579)
- Junnian Zheng
- Shunshun Bao
Institutions
- Xuzhou Medical College (CN)
- Jinan Central Hospital (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Breast Cancer Research
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1186/s13058-025-02193-5
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00