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Published on: May 27, 2016
Ginseng-Derived Exosomes Attenuate Immune Evasion in NSCLC via PD-L1 Modulation
Lin-Jia Zhu1, Xiao-Qiang Chen2, Qiu-Yan Lin2
1Department of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, 325200, People's Republic of China.
Background:
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. While PD-1/PD-L1 immune checkpoint blockade has shown promise, its efficacy is often limited by tumor-induced immune evasion. Ginseng-derived exosomes (G-Exos), as natural plant-based nanocarriers, may offer a novel strategy for immunomodulation. This study investigated the potential of G-Exos to regulate PD-L1 expression and enhance anti-tumor immunity in NSCLC.
Methods:
Exosomes were isolated from ginseng cell cultures and characterized via transmission electron microscopy and nanoparticle tracking analysis. Uptake by NSCLC cells was confirmed using PKH26 labeling. In vitro, NSCLC cells were co-cultured with activated T cells to evaluate cytotoxicity (colony formation), cytokine secretion [enzyme-linked immunosorbent assay (ELISA)], and T-cell activation (flow cytometry). PD-L1 expression was assessed by quantitative polymerase chain reaction (qPCR) and Western blot. In vivo, C57BL/6 mice (n = 20) bearing Lewis lung carcinoma (LLC) tumors were randomized into four groups (n = 5/group): PBS, G-Exos (10 μg), anti-PD-L1 (8 μg), or combination therapy. Treatments were administered intravenously every other day for 20 days. Tumor growth was measured, and tissues were analyzed by immunohistochemistry and flow cytometry.
Results:
G-Exos were efficiently internalized by NSCLC cells and demonstrated immunostimulatory properties in vitro. They enhanced T-cell-mediated cytotoxicity, as reflected by reduced tumor colony formation, and promoted immune activation, evidenced by increased IL-2 and IFN-γ secretion and a higher proportion of CD8⁺ T cells expressing TNF-α and perforin. Mechanistically, G-Exos downregulated PD-L1 expression at both transcriptional and translational levels in NSCLC cells. In vivo, G-Exos treatment significantly inhibited tumor growth and, when combined with anti-PD-L1 monoclonal antibody, exhibited a synergistic effect characterized by greater tumor suppression and increased infiltration of cytotoxic CD8⁺ T cells in the tumor microenvironment.
Conclusion:
Ginseng-derived exosomes downregulate PD-L1 and enhance T-cell function, counteracting immune evasion in NSCLC. Their synergy with anti-PD-L1 therapy supports their potential as adjuvant nanotherapeutics in cancer immunotherapy.
Insights
Ginseng-derived exosomes (G-Exos) reduce PD-L1 expression and boost T-cell activity in non-small cell lung cancer (NSCLC). Combining G-Exos with anti-PD-L1 therapy shows synergistic effects, offering a promising nanotherapeutic approach for cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Nanomedicine
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
- Current PD-1/PD-L1 immune checkpoint blockade efficacy is limited by tumor immune evasion.
- Ginseng-derived exosomes (G-Exos) present a novel plant-based nanocarrier strategy for immunomodulation in NSCLC.
Purpose of the Study:
- To investigate the potential of G-Exos to modulate PD-L1 expression in NSCLC.
- To evaluate the capacity of G-Exos to enhance anti-tumor immunity.
- To assess the synergistic effects of G-Exos with anti-PD-L1 therapy in NSCLC models.
Main Methods:
- G-Exos were isolated and characterized; NSCLC cell uptake was confirmed.
- In vitro assays assessed T-cell cytotoxicity, cytokine secretion (IL-2, IFN-γ), and T-cell activation markers.
- In vivo studies in Lewis lung carcinoma (LLC) mouse models evaluated tumor growth inhibition and immune cell infiltration under different treatment regimens (PBS, G-Exos, anti-PD-L1, combination).
Main Results:
- G-Exos were internalized by NSCLC cells and demonstrated immunostimulatory effects in vitro, enhancing T-cell cytotoxicity and cytokine production.
- G-Exos significantly downregulated PD-L1 expression in NSCLC cells at both transcriptional and translational levels.
- In vivo, G-Exos inhibited tumor growth, and combination therapy with anti-PD-L1 showed synergistic tumor suppression and increased CD8+ T cell infiltration.
Conclusions:
- Ginseng-derived exosomes effectively downregulate PD-L1 and enhance T-cell function, counteracting immune evasion in NSCLC.
- The observed synergy between G-Exos and anti-PD-L1 therapy highlights their potential as adjuvant nanotherapeutics.
- G-Exos represent a promising strategy for improving cancer immunotherapy outcomes in NSCLC.
