# Glycyrrhiza polysaccharide-adjuvanted liposomal vaccine potentiates tumor immunotherapy through lymph node-targeted modulation of the DC-T cell axis

**Authors:** Xiaopan Yao, Keqing Zhang, XiaoKun Zhang, Shengxin Lu, Jinyuan Hu, Yuexuan Wang, Jiayi Lin, Ye Wu, Weidong Zhang, Hongzhuan Chen, Xia Liu, Bei Wang, Xin Luan

PMC · DOI: 10.1186/s13046-025-03601-6 · Journal of Experimental & Clinical Cancer Research : CR · 2025-11-28

## TL;DR

A new vaccine adjuvant made from licorice polysaccharides boosts cancer immunotherapy by targeting immune cells in lymph nodes.

## Contribution

NGUP is a novel adjuvant that enhances tumor immunotherapy via lymph node-targeted dendritic cell activation.

## Key findings

- NGUP activates dendritic cells through the TLR4/MyD88/TRAF6/NF-κB pathway.
- NGUPL@OVA promotes strong CD8+ T cell activation and long-term immune memory.
- NGUPL@OVA inhibits melanoma growth without toxic side effects in mouse models.

## Abstract

A key challenge in cancer immunotherapy is that tumor vaccines formulated with conventional aluminum adjuvants often fail to elicit potent cellular immunity and sustained antitumor responses. Glycyrrhizae polysaccharides (NGUP), characterized by significant immunomodulation, multi-target antitumor efficacy, and low toxicity, represent promising candidates for next-generation vaccine adjuvants.

We employed transcriptome analysis, quantitative real-time PCR, and Western blot assays to investigate the mechanism of NGUP in activating bone marrow-derived dendritic cells in vitro. Using confocal microscopy, small animal in vivo imaging, and flow cytometry, we examined the process of tumor antigen-specific T cell response activation by the liposomal vaccine (NGUPL@OVA) in vivo. The efficacy of NGUPL@OVA was evaluated in murine melanoma models (B16-OVA and B16-F10) through immunohistochemistry, immunofluorescence and H&E staining.

NGUP activates dendritic cells through the TLR4/MyD88/TRAF6/NF-κB signaling pathway. NGUPL@OVA demonstrates efficient lymph node targeting capacity, significantly enhancing dendritic cell maturation and antigen cross-presentation, thereby promoting robust CD8+ T cell activation and inducing potent cellular immune responses with long-term immunological memory. In both prophylactic and therapeutic settings, NGUPL@OVA exhibits significant melanoma growth inhibition without observable toxic side effects.

NGUP as a novel vaccine adjuvant for cancer immunotherapy effectively overcomes key limitations of conventional aluminum adjuvants, including weak induction of cell-mediated immunity and significant adverse effects, while exhibiting superior immune-stimulating properties.

The online version contains supplementary material available at 10.1186/s13046-025-03601-6.

## Linked entities

- **Genes:** TLR4 (toll like receptor 4) [NCBI Gene 7099], MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615], TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790]
- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}
- **Diseases:** cancer (MESH:D009369), melanoma (MESH:D008545), toxicity (MESH:D064420)
- **Chemicals:** H&amp;E (MESH:D006371), aluminum (MESH:D000535), Glycyrrhiza polysaccharide (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** B16-OVA — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_WM78), B16-F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12764037/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12764037/full.md

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Source: https://tomesphere.com/paper/PMC12764037