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

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. γδ T cell-based immunotherapies are limited by the reduced expansion and activation of the T cells ex vivo. Here the authors show that garlic nanoparticles can activate IFNγ-producing γδ T cells directly in the intestine, before they translocate to extraintestinal tumours, where they can synergize with anti-PD-L1 therapy, inducing robust antitumour immunity.