Abstract
Objective
To investigate whether Fuzheng Jiedu Xiaoji Formula (FZJDXJ) reverses immunosuppression in HBV
+
hepatocellular carcinoma (HCC) by reprogramming CD8
+
T-cell glycolysis and enhance antitumor immunity.
Methods
A translational study was conducted with 80 HBV
+
HCC patients, Hepa1-6 tumor-bearing mouse models and
in vitro
CD8
+
T-cell assays. Flow cytometry, GC/LC-MS metabolomics, Western blot and functional experiments were used to detect CD8
+
T-cell immunophenotype, glycolytic metabolism and antitumor activity. A 1-year overall survival (OS) prediction framework was constructed and validated.
Results
FZJDXJ increased peripheral CD8
+
T-cell frequency, downregulated exhaustion markers (PD-1/CTLA-4/TIM-3) and upregulated glycolysis-related metabolites in patients, with metabolites correlating with CD8
+
T-cell function. In mice, FZJDXJ suppressed tumor growth, enhanced tumor-infiltrating CD8
+
T-cell cytotoxicity and glycolytic flux (GLUT1/HK2/PFKFB3/PKM2 upregulation).
In vitro
, FZJDXJ-containing serum dose-dependently promoted CD8
+
T-cell glucose uptake and glycolytic molecule expression. The OS prediction framework had high discriminatory power (AUC=0.946). No severe safety signals were observed.
Conclusion
FZJDXJ alleviates CD8
+
T-cell exhaustion by enhancing glycolysis to strengthen antitumor immunity in HBV
+
HCC. Immunometabolism is a promising target for herbal interventions, and glycolysis-immune features may serve as prognostic stratifiers. Prospective trials and ICI combination studies are warranted.