Cancer cachexia as an immunometabolic syndrome: targeting the immunometabolic interface with traditional Chinese Medicine monomers and formulas.

Authors

Baoyi Ni, Shuhang Wang, Xi Zhang, Zhu Liu, Weiming Wang, Huan He, Jia Wang

Published in

Frontiers in immunology. Volume 17. Pages 1934109. Epub Sep 22, 2026.

Abstract

Cancer cachexia is conventionally viewed as muscle wasting but is increasingly recognized as a tumor-driven immunometabolic syndrome. This systemic disorder is characterized by a vicious cycle of metabolic dysregulation, systemic inflammation, and immune evasion, severely compromising the efficacy of immune checkpoint inhibitors (ICIs). Conventional single-target therapies have largely failed to disrupt this redundant pathological network. Here, we comprehensively review the therapeutic potential of Traditional Chinese Medicine (TCM) as multi-target network modulators acting at the immunometabolic interface. At the micro-level, TCM-derived monomers (such as curcumin, andrographolide, and epigallocatechin gallate (EGCG)) bidirectionally target this interface by concurrently suppressing muscle catabolism (via ubiquitin-proteasome and ferroptosis pathways) and reprogramming the immunosuppressive tumor immune microenvironment (TIME) (downregulating PD-L1 and inhibiting MDSCs/Tregs). At the macro-level, chromatographically characterized multi-herb formulas offer systemic recalibration via the gut-muscle-immune axis, utilizing microbial metabolites to restore intestinal barrier integrity, curb systemic inflammation, and epigenetically reinvigorate exhausted CD8+ T cells. Clinically, integrating TCM with ICIs presents a promising synergistic strategy to restore patient eligibility, optimize immunotherapeutic responses, and mitigate treatment-related adverse events. This review provides a mechanistic framework for positioning TCM as a potential systemic adjuvant to break the cachexia-immunosuppression loop in modern oncology.

PMID:
42840956
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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