Herb-derived immunometabolic modulators: traditional Chinese medicine at the crossroads of metabolism and antitumor immunity.

Abstract

Background: Traditional Chinese Medicine (TCM) has long been applied in oncology to "support vital Qi and eliminate pathogenic factors", yet its place within modern immunometabolic therapy is still not clearly defined. Tumor, stromal, and immune cells are now understood to be organized around several recurrent metabolic axes, including glycolysis-lactate, mitochondrial stress and immunogenic cell death (ICD), lipid-bile-acid signaling, and redox balance. Clarifying how herb-based formulas, isolated compounds, and contemporary delivery systems influence these axes may provide a mechanistic foundation for integrating TCM into precision cancer treatment.

Main body: This narrative review brings together ethnopharmacological knowledge with pharmacological and mechanistic studies, omics-based profiling, and emerging nanomedicine reports that examined TCM-derived interventions with defined metabolic and immune outcomes in solid tumors. We first outline how metabolic reprogramming of the tumor microenvironment (TME) shapes major immune populations, including dendritic cells (DCs), CD8⁺ T cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and NK/NKT cells. We then arrange representative herb-derived agents along four immunometabolic axes. Across Axis I-IV, multiple prescriptions and monomers have been reported to attenuate tumor glycolytic flux and lactate burden, induce mitochondrial damage and ferroptosis-linked ICD, normalize lipid-bile-acid-centered myeloid niches, and improve DC and T-cell metabolic fitness. Examples include Astragalus-based formulas, Gegen Qinlian decoction (GQD), ginsenosides, berberine, licochalcone A, emodin, celastrol-Rg3 and iron-based nanoplatforms, Jianpi Jiedu and Jianpi Huayu decoctions, Compound Kushen Injection, Compound Fuling Granule, Hochu-ekki-to, Kejinyan decoction, Huaier, Ganoderma polysaccharides, Shenqi Yiqi Capsule, and polysaccharide-loaded vesicles or microneedles. Finally, we relate these axes to classical TCM doctrines such as Fuzheng Quxie, Tiaogan Hepi, and Peiben Chuzhuo, proposing a clinically oriented, syndrome-informed framework.

Conclusion: TCM-derived interventions can be systematically positioned along four convergent immunometabolic axes that coordinate interactions between tumors and the immune system. Considering TCM as an immunometabolic co-therapy highlights its potential to convert "cold" tumors into "hot" lesions, deepen responses to chemo-, radio- and immunotherapy, and, in some contexts, improve treatment tolerance. Future studies should emphasize rigorous mechanistic dissection, standardized and chemically defined formulations, biomarker-guided patient selection, and well-designed prospective clinical trials to translate this axis-based framework into precision integrative oncology. However, most TCM-derived immunometabolic interventions remain incompletely validated, and their translation will require axis-matched biomarkers, rigorous safety assessment, and prospective clinical validation.