Related Experiment Video
Updated: Jul 14, 2026
Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine
Published on: October 13, 2023
Shuyu Wan Potentiates PD-1 Inhibitor Efficacy in Non-Small Cell Lung Cancer: Integrated Bioinformatics and
Tianqing Sang1,2,3, Yajing Li1,3, Qihan He1,2,3
1Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
Background:
Therapeutic heterogeneity limits the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Shuyu Wan (SYW), a classic TCM formula, has shown potential in modulating gut microbiota (GM) and enhancing immunotherapy, yet its synergistic mechanism with PD-1 inhibitors remains unclear.
Materials And Methods:
SYW components were identified by UPLC-MS. NSCLC-related targets were integrated with SYW targets for pathway enrichment, and molecular docking validated component-target binding. NSCLC syngeneic mice were treated with SYW and/or PD-1 inhibitor (RMP1-14). Tumor growth, histopathology, serum cytokines, tumor-infiltrating CD8+T cell subsets (flow cytometry), PD-1/PD-L1 expression and co-localization (immunofluorescence), GM composition (16S rRNA), and metabolomics were assessed. FMT verified the role of GM-TME crosstalk.
Results:
SYW monotherapy showed no significant tumor inhibition, whereas SYW combined with PD-1 inhibitor dose-dependently suppressed NSCLC growth. The combination reduced PD-1 expression and PD-1/PD-L1 co-localization, elevated serum IL-12, IFN-γ, and TNF-α, increased total tumor-infiltrating CD8+ T cells, decreased PD-1+ and TIM-3+ exhausted subsets, and expanded IFN-γ+ and Granzyme B+ effector subsets. Concurrently, it reshaped GM (increased Bacillota, decreased Patescibacteria) and altered metabolites (L-glycine, L-proline). These effects were abolished in antibiotic treated mice and restored by FMT, suggesting GM-TME crosstalk as essential.
Conclusion:
SYW acts as a microbiota-dependent immune sensitizer that potentiates PD-1 inhibitor efficacy in NSCLC by remodeling GM and enhancing effector CD8+ T cell infiltration while reducing exhaustion. GM-TME crosstalk is the potential mechanism, supporting SYW as an adjunct to PD-1 blockade in NSCLC therapy.
Insights
Shuyu Wan (SYW) enhances PD-1 inhibitor efficacy in non-small cell lung cancer (NSCLC) by modulating gut microbiota and boosting CD8+ T cell responses. This traditional Chinese medicine formula shows promise in overcoming therapeutic heterogeneity in NSCLC immunotherapy.
Area of Science:
- Immunology
- Oncology
- Microbiology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) efficacy in non-small cell lung cancer (NSCLC) is limited by therapeutic heterogeneity.
- Shuyu Wan (SYW), a traditional Chinese medicine formula, may enhance immunotherapy by modulating gut microbiota (GM).
- The synergistic mechanism of SYW with PD-1 inhibitors in NSCLC is not well understood.
Purpose of the Study:
- To investigate the synergistic mechanism of Shuyu Wan (SYW) combined with PD-1 inhibitors in non-small cell lung cancer (NSCLC).
- To elucidate the role of gut microbiota (GM) and gut microbiota-tumor microenvironment (TME) crosstalk in the combined therapeutic effect.
Main Methods:
- Component identification of SYW using UPLC-MS and target analysis.
- In vivo studies using NSCLC syngeneic mouse models treated with SYW and/or PD-1 inhibitor.
- Assessment of tumor growth, immune cell infiltration (CD8+ T cells), PD-1/PD-L1 expression, GM composition, and metabolomics.
- Fecal microbiota transplantation (FMT) and antibiotic treatment to verify the role of GM-TME crosstalk.
Main Results:
- Combined SYW and PD-1 inhibitor treatment dose-dependently suppressed NSCLC growth.
- The combination therapy enhanced effector CD8+ T cell infiltration and reduced exhausted subsets, while increasing key cytokines (IL-12, IFN-γ, TNF-α).
- SYW reshaped GM composition and altered host metabolites, with these effects being dependent on GM and essential for therapeutic efficacy, as confirmed by FMT.
Conclusions:
- Shuyu Wan acts as a microbiota-dependent immune sensitizer, potentiating PD-1 inhibitor efficacy in NSCLC.
- The mechanism involves remodeling GM and enhancing effector CD8+ T cell responses while reducing exhaustion.
- GM-TME crosstalk is crucial, supporting SYW as an adjunct therapy for NSCLC treated with PD-1 blockade.
