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Oral administration of garlic-derived nanoparticles improves cancer immunotherapy by inducing intestinal IFNγ-producing γδ T cells

Nature Nanotechnology volume 19, pages 1569–1578 (2024)Cite this article

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Abstract

Gamma-delta (γδ) T cell-based cancer immunotherapies represent a promising avenue for cancer treatment. However, their development is challenged by the limited expansion and differentiation of the cells ex vivo. Here we induced the endogenous expansion and activation of γδ T cells through oral administration of garlic-derived nanoparticles (GNPs). We found that GNPs could significantly promote the proliferation and activation of endogenous γδ T cells in the intestine, leading to generation of large amount of interferon-γ (IFNγ). Moreover GNP-treated mice showed increased levels of chemokine CXCR3 in intestinal γδ T cells, which can drive their migration from the gut to the tumour environment. The translocation of γδ T cells and IFNγ from the intestine to extraintestinal subcutaneous tumours remodels the tumour immune microenvironment and synergizes with anti-PD-L1, inducing robust antitumour immunity. Our study delineates mechanistic insight into the complex gut–tumour interactome and provides an alternative approach for γδ T cell-based immunotherapy.

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Fig. 1: Preparation and characterization of GNPs.
Fig. 2: Biodistribution of GNPs after oral administration.
Fig. 3: GNPs induced intestinal IFNγ-producing γδT cells.
Fig. 4: GNPs reversed the immune microenvironment of solid tumours at distant sites.
Fig. 5: Oral administration of GNPs improves cancer immune checkpoint blockade therapy efficacy.

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Data availability

Source data are provided with this paper. The authors declare that all other data supporting the findings of this study are available within the paper or Supplementary Information.

Code availability

Single-cell RNA-sequencing data have been deposited at Sequence Read Archive (SRA). SRA records are accessible with the following link: https://www.ncbi.nlm.nih.gov/sra/PRJNA1102105.

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Acknowledgements

This work was supported by the National Key R&D Program of China (grant number 2022YFB3808100) and the National Natural Science Foundation of China (grant numbers 32371476 and T2321005). This work was partly supported by the Collaborative Innovation Center of Suzhou Nano Science and Technology, the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the 111 Project.

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Authors and Affiliations

  1. Laboratory for Biomaterial and ImmunoEngineering, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, China

    Jialu Xu, Yue Yu, Yue Zhang, Huaxing Dai, Qianyu Yang, Beilei Wang, Qingle Ma, Yitong Chen, Fang Xu, Zhuang Liu & Chao Wang

  2. Medical College of Soochow University, Suzhou, China

    Xiaolin Shi

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Contributions

C.W. and J.X. designed the project. J.X. performed the experiments, collected the data, analysed and interpreted the data, and wrote the first version of the paper. All the authors discussed the results and implications and edited the paper at all stages.

Corresponding authors

Correspondence to Zhuang Liu or Chao Wang.

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Competing interests

C.W. and J.X. are inventors on a pending patent related to the technology described here, filed by Soochow University (number CN202310634131.4, filed 12 September 2023). The other authors declare no competing interests.

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Xu, J., Yu, Y., Zhang, Y. et al. Oral administration of garlic-derived nanoparticles improves cancer immunotherapy by inducing intestinal IFNγ-producing γδ T cells. Nat. Nanotechnol. 19, 1569–1578 (2024). https://doi.org/10.1038/s41565-024-01722-1

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