越来越多的证据表明，细菌外膜囊泡（OMVs）产生的免疫激活可以启动强效的抗肿瘤免疫反应，促进对恶性细胞的识别和消灭。目前，这种反应的相关途径仍然知之甚少，尽管已提出了固有型细胞（如γδT细胞）在其中发挥了一定作用。从健康捐赠者的外周血单核细胞（PBMCs）与E. coli MG1655 Δpal ΔlpxM OMVs进行共培养，并通过细胞标记物表达和细胞因子产生研究对应的免疫激活情况。OMV激活的γδT细胞与癌细胞系共培养以确定细胞毒性。 外膜囊泡诱导了广泛的炎症反应，γδT细胞被观察到是OMV激发后增殖的主要细胞类型。值得注意的是，大多数γδT细胞属于已知对细菌代谢产物和肿瘤细胞上的应激标记物具有反应性的Vγ9Vδ2类型。我们观察到，在经过OMV介导扩增后，Vγ9Vδ2 T细胞对乳腺癌和白血病细胞系（分别为SkBr3和Nalm6）表现出强大的溶菌活性。 我们的研究首次发现，OMV的挑战刺激了Vγ9Vδ2 T细胞的扩增，随后呈现出抗肿瘤能力。我们提出，OMV介导的免疫激活利用了Vγ9Vδ2 T细胞具有的抗微生物/抗肿瘤能力，这为未来改善治疗方案提供了可行的途径。 版权所有©2023 Firth, Sun, George, Huang, Bajaj-Elliott, and Gustafsson.

Increasing evidence suggests the immune activation elicited by bacterial outer-membrane vesicles (OMVs) can initiate a potent anti-tumor immunity, facilitating the recognition and destruction of malignant cells. At present the pathways underlying this response remain poorly understood, though a role for innate-like cells such as γδ T cells has been suggested.Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with E. coli MG1655 Δpal ΔlpxM OMVs and corresponding immune activation studied by cell marker expression and cytokine production. OMV-activated γδ T cells were co-cultured with cancer cell lines to determine cytotoxicity.The vesicles induced a broad inflammatory response with γδ T cells observed as the predominant cell type to proliferate post-OMV challenge. Notably, the majority of γδ T cells were of the Vγ9Vδ2 type, known to respond to both bacterial metabolites and stress markers present on tumor cells. We observed robust cytolytic activity of Vγ9Vδ2 T cells against both breast and leukaemia cell lines (SkBr3 and Nalm6 respectively) after OMV-mediated expansion.Our findings identify for the first time, that OMV-challenge stimulates the expansion of Vγ9Vδ2 T cells which subsequently present anti-tumor capabilities. We propose that OMV-mediated immune activation leverages the anti-microbial/anti-tumor capacity of Vγ9Vδ2 T cells, an axis amenable for improved future therapeutics.Copyright © 2023 Firth, Sun, George, Huang, Bajaj-Elliott and Gustafsson.