As an emerging cancer treatment, γδ T cell-based immunotherapy has garnered widespread attention. However, this therapy still faces many issues that need to be addressed. For instance, achieving tumor control typically requires multiple infusions of γδ T cells in patients, and the expansion of γδ T cells with proliferative and cytotoxic capabilities remains costly, time-consuming, and technically demanding. Therefore, producing large quantities of natural or engineered γδ T cells is highly challenging. If direct in vivo activation and expansion of γδ T cells could be achieved, it might overcome the aforementioned limitations, thereby enhancing the clinical efficacy and safety of γδ T cell immunotherapy.
Previous studies have shown that supplementing the diet with garlic extracts can increase γδ T cell activity. However, this immunostimulatory effect is rather weak, and the nutritional role of garlic in cancer treatment is very limited. To address this issue, a recent collaborative study by Professor Wang Chao and Professor Liu Zhuang's team from the Institute of Functional Nano & Soft Materials (FUNSOM) at Soochow University found that garlic-derived nanoparticles (GNPs) can enhance the efficacy of tumor immune checkpoint blockade therapy against solid tumors by significantly inducing γδ T cells in the gut to produce interferon IFNγ. Compared to consuming garlic or using isolated active molecules from garlic, GNPs with nanostructures (~100nm) are more effective at activating γδ T cells in the gut when administered orally, demonstrating the unique role of nanostructured active substances in amplifying immune responses.
We found that GNPs significantly promote the proliferation and activation of endogenous γδ T cells in the gut, leading to a substantial production of IFNγ. Moreover, the level of the chemokine receptor CXCR3 in the gut γδ T cells of GNP-treated mice increased, driving their migration from the gut to the tumor environment. The transfer of γδ T cells and IFNγ from the gut to extragastrointestinal subcutaneous tumors remodels the tumor immune microenvironment and synergizes with anti-PD-L1 to induce a potent antitumor immune response. Our research unveils the potential complex interactions between the gut and tumors, providing a new approach for γδ T cell-based immunotherapy. The related research findings were published online in Nature Nanotechnology on July 25, 2024, with the first author being our institute's graduated PhD student Xu Jialu.
Link to paper:https://www.nature.com/articles/s41565-024-01722-1
Title:Oral administration of garlic-derived nanoparticles improves cancer immunotherapy by inducing intestinal IFNγ-producing γδ T cells
Authors:Jialu Xu, Yue Yu, Yue Zhang, Huaxing Dai, Qianyu Yang, Beilei Wang, Qingle Ma, Yitong Chen, Fang Xu, Xiaolin Shi, Zhuang Liu* & Chao Wang*
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.
Editor: Danting Xiang, Xin Du