Lactate Activates <scp>TGF</scp> ‐ <i>β</i> / <scp>SNAIL</scp> Signaling to Drive <scp>M2</scp> Macrophage Polarization and <scp>CD8</scp> <sup>+</sup> T Cell Exhaustion in Breast Cancer
), while TGF-β inhibition (SB431542) reversed these effects. Mechanistically, lactate-induced TGF-β/SNAIL signaling promoted EMT in cancer cells and created an immunosuppressive TME. These findings establish lactate as a critical metabolic regulator that coordinates macrophage polarization and T cell exhaustion through the TGF-β/SNAIL axis, highlighting this pathway as a promising therapeutic target for breast cancer immunotherapy.
Authors
- Zhisheng Tian
- Peiling Zhu
- Zehui Mi (ORCID: https://orcid.org/0009-0003-5774-2769)
- Haiying Liao
- Ying Wang
Institutions
- Hebei Medical University (CN)
- Second Hospital of Hebei Medical University (CN)
Publication Details
- Journal
- The FASEB Journal
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1096/fj.202502538rr
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00