Disruption of the NKG2A:HLA-E immune checkpoint axis to enhance NK cell activation against Cancer
Disruption of the NKG2A:HLA-E immune checkpoint axis to enhance NK cell activation against Cancer
Ligation of the inhibitory receptor NKG2A by its ligand HLA-E negatively regulates the activation of natural killer (NK) cells, as well as subsets of CD8+ T cells and innate T cell populations. NKG2A has recently become a novel immune checkpoint target for the treatment of cancer and direct antibody mediated blockade of NKG2A function is currently under assessment in two phase 3 clinical trials. In addition to direct targeting, the NKG2A:HLA-E axis can also be disrupted indirectly via multiple different targeted cancer agents that were not previously recognised to possess immunomodulatory properties. Increased understanding of immune cell modulation by targeted cancer therapies will allow for the design of rational and more efficacious drug combination strategies to improve cancer patient outcomes. In this review, we summarise and discuss the various strategies currently in development which either directly or indirectly disrupt the NKG2A:HLA-E interaction to enhance NK cell activation against cancer.
Fisher, Jack G.
5d9176a9-c6a6-4234-a178-3054eee07eb4
Doyle, Amber D. P.
eff9eb33-8e3e-4597-9ef1-7b1015a5f343
Graham, Lara V.
4a7bbe46-4e8e-476d-87f5-5c83304a5293
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Blunt, Matthew D.
b1109de3-6045-4bc3-bd77-6cf26504697d
23 November 2022
Fisher, Jack G.
5d9176a9-c6a6-4234-a178-3054eee07eb4
Doyle, Amber D. P.
eff9eb33-8e3e-4597-9ef1-7b1015a5f343
Graham, Lara V.
4a7bbe46-4e8e-476d-87f5-5c83304a5293
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Blunt, Matthew D.
b1109de3-6045-4bc3-bd77-6cf26504697d
Fisher, Jack G., Doyle, Amber D. P., Graham, Lara V., Khakoo, Salim I. and Blunt, Matthew D.
(2022)
Disruption of the NKG2A:HLA-E immune checkpoint axis to enhance NK cell activation against Cancer.
Vaccines, 10 (12), [1993].
(doi:10.3390/vaccines10121993).
Abstract
Ligation of the inhibitory receptor NKG2A by its ligand HLA-E negatively regulates the activation of natural killer (NK) cells, as well as subsets of CD8+ T cells and innate T cell populations. NKG2A has recently become a novel immune checkpoint target for the treatment of cancer and direct antibody mediated blockade of NKG2A function is currently under assessment in two phase 3 clinical trials. In addition to direct targeting, the NKG2A:HLA-E axis can also be disrupted indirectly via multiple different targeted cancer agents that were not previously recognised to possess immunomodulatory properties. Increased understanding of immune cell modulation by targeted cancer therapies will allow for the design of rational and more efficacious drug combination strategies to improve cancer patient outcomes. In this review, we summarise and discuss the various strategies currently in development which either directly or indirectly disrupt the NKG2A:HLA-E interaction to enhance NK cell activation against cancer.
Text
vaccines-10-01993-v2
- Version of Record
More information
Accepted/In Press date: 22 November 2022
Published date: 23 November 2022
Identifiers
Local EPrints ID: 478349
URI: http://eprints.soton.ac.uk/id/eprint/478349
ISSN: 2076-393X
PURE UUID: 2e704cdb-159d-498c-aaf6-33f16bf7750e
Catalogue record
Date deposited: 28 Jun 2023 17:00
Last modified: 17 Mar 2024 04:04
Export record
Altmetrics
Contributors
Author:
Jack G. Fisher
Author:
Amber D. P. Doyle
Author:
Lara V. Graham
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics