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.

基于 γ-δ （γδ） T 细胞的癌症免疫疗法代表了癌症治疗的一条有前途的途径。然而，它们的发育受到细胞离体扩增和分化受限的挑战。在这里，我们通过口服大蒜衍生的纳米颗粒 （GNP） 诱导 γδ T 细胞的内源性扩增和活化。我们发现 GNPs 可以显着促进肠道内源性 γδ T 细胞的增殖和活化，导致大量干扰素-γ （IFNγ） 的产生。此外，GNP 处理的小鼠在肠道 γδ T 细胞中显示出趋化因子 CXCR3 水平升高，这可以驱动它们从肠道迁移到肿瘤环境。γδ T 细胞和 IFNγ 从肠道转移到肠外皮下肿瘤，重塑肿瘤免疫微环境，并与抗 PD-L1 协同作用，诱导强大的抗肿瘤免疫。我们的研究描述了对复杂肠道-肿瘤相互作用组的机制见解，并为基于 γδ T 细胞的免疫疗法提供了一种替代方法。