SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2(+) γδ T cell cytotoxicity in a perforin-dependent manner.

Fowler, DW; Copier, J; Dalgleish, AG; Bodman-Smith, MD (2017) Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2(+) γδ T cell cytotoxicity in a perforin-dependent manner. Cancer Immunol Immunother, 66 (9). pp. 1205-1215. ISSN 1432-0851 https://doi.org/10.1007/s00262-017-2011-1
SGUL Authors: Bodman-Smith, Mark Duncan Copier, John Paul Dalgleish, Angus George Fowler, Daniel William

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
[img]
Preview
PDF Accepted Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA. We differentiated peripheral blood monocytes from healthy donors into Mϕs and then treated them with IFN-γ or IL-4 to generate M1 and M2 Mϕs, respectively. We characterised these Mϕs based on their phenotype and cytokine production and then tested whether ZA rendered them susceptible to Vδ2(+) T cell cytotoxicity. Consistent with the literature, IFN-γ-treated Mϕs expressed higher levels of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mϕs expressed higher levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated with ZA, both M1 and M2 Mϕs became susceptible to Vδ2(+) T cell cytotoxicity. Vδ2(+) T cells expressed perforin and degranulated in response to ZA-treated Mϕs as shown by mobilisation of CD107a and CD107b to the cell surface. Furthermore, cytotoxicity towards ZA-treated Mϕs was sensitive-at least in part-to the perforin inhibitor concanamycin A. These findings suggest that ZA can render M1 and M2 Mϕs susceptible to Vδ2(+) T cell cytotoxicity in a perforin-dependent manner, which has important implications regarding the use of ZA in cancer immunotherapy.

Item Type: Article
Additional Information: © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Cytotoxicity, Macrophage, Vδ2+ T cell, Zoledronic acid, γδ T cell, gamma delta T cell, V delta 2(+) T cell, Macrophage, Zoledronic acid, Cytotoxicity, Immunology, 1107 Immunology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Cancer Immunol Immunother
ISSN: 1432-0851
Language: eng
Dates:
DateEvent
September 2017Published
13 May 2017Published Online
2 May 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDInstitute for Cancer Vaccines and ImmunotherapyUNSPECIFIED
PubMed ID: 28501938
Web of Science ID: WOS:000408717200010
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108805
Publisher's version: https://doi.org/10.1007/s00262-017-2011-1

Actions (login required)

Edit Item Edit Item