ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1615631
This article is part of the Research TopicCancer prevention and therapy using herbal formulations of natural immune modulatorsView all 3 articles
Yiai Fuzheng Decoction Inhibits Triple-Negative Breast Cancer by Remodeling the Immune Microenvironment
Provisionally accepted
- 1Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, Hebei Province, China
- 3Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China
- 4Nanchang University, Nanchang, Jiangxi Province, China
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Objective: This study aimed to examine the potential anticancer properties of Yiai Fuzheng decoction (YFD), along with its mechanism of action against triple-negative breast cancer (TNBC). Methods: A TNBC mouse model was established by inoculating 4T1 cells into the 4th mammary fat pad. Micropositron emission tomography (micro-PET), hematoxylin and eosin (HE) staining, immunohistochemistry, immunofluorescence assays, flow cytometry, and western blotting were used to assess the therapeutic effects of YFD. The components of YFD were identified via UHPLC-Q/Orbitrap MS. Nontargeted metabolomic analysis was performed to identify changes in tumor metabolites via gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS). The Illumina sequencing platform was used to identify differentially expressed genes in the tumors. Results: A total of 20 bioactive components of YFD were screened and identified. We found that YFD treatment resulted in a substantial increase in CD4+ and CD8+ T cells, a reduction in myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and an increase in the M1/M2 ratio of TAMs in tumors. These changes create a tumor-suppressive microenvironment that inhibits tumor growth and metastasis in TNBC mice. YFD can affect various immune regulatory pathways, such as inactivation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1 and 2 (MEK/ERK1/2) pathway. Additionally, metabolomic analysis suggested that YFD could reprogram several altered metabolic pathways, including the urea cycle; metabolism of arginine and proline; pyruvate; the Warburg effect; D-arginine; and D-ornithine, glutamate, glycine, serine, and tryptophan, to suppress cancer progression. Conclusion: Our findings provide preclinical evidence that supports the application of YFD in TNBC treatment.
Keywords: Yiai Fuzheng decoction, Triple-negative breast cancer, Tumor Microenvironment, Transcriptomic profiling, metabonomic profiling
Received: 21 Apr 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Yu, Jia, Chen, Li, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ying-Wen Zhang, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.