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Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity
BACKGROUND: 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, t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388717/ https://www.ncbi.nlm.nih.gov/pubmed/37529036 http://dx.doi.org/10.3389/fimmu.2023.1198996 |
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author | Firth, Jack Sun, Jingjing George, Vaques Huang, Jian-Dong Bajaj-Elliott, Mona Gustafsson, Kenth |
author_facet | Firth, Jack Sun, Jingjing George, Vaques Huang, Jian-Dong Bajaj-Elliott, Mona Gustafsson, Kenth |
author_sort | Firth, Jack |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-10388717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103887172023-08-01 Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity Firth, Jack Sun, Jingjing George, Vaques Huang, Jian-Dong Bajaj-Elliott, Mona Gustafsson, Kenth Front Immunol Immunology BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Frontiers Media S.A. 2023-07-17 /pmc/articles/PMC10388717/ /pubmed/37529036 http://dx.doi.org/10.3389/fimmu.2023.1198996 Text en Copyright © 2023 Firth, Sun, George, Huang, Bajaj-Elliott and Gustafsson https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Firth, Jack Sun, Jingjing George, Vaques Huang, Jian-Dong Bajaj-Elliott, Mona Gustafsson, Kenth Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title | Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title_full | Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title_fullStr | Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title_full_unstemmed | Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title_short | Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity |
title_sort | bacterial outer-membrane vesicles promote vγ9vδ2 t cell oncolytic activity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388717/ https://www.ncbi.nlm.nih.gov/pubmed/37529036 http://dx.doi.org/10.3389/fimmu.2023.1198996 |
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