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The Paradoxical Role of NKG2D in Cancer Immunity

Authors :
Sam Sheppard
Amir Ferry
Joana Guedes
Nadia Guerra
Wellcome Trust
AstraZeneca UK Limited
Source :
Frontiers in Immunology, Vol 9 (2018), Frontiers in Immunology
Publication Year :
2018
Publisher :
Frontiers Media S.A., 2018.

Abstract

The activating receptor NKG2D and its ligands are recognized as a potent immune axis that controls tumor growth and microbial infections. With regards to cancer surveillance, various studies have demonstrated the antitumor function mediated by NKG2D on natural killer cells and on conventional and unconventional T cells. The use of NKG2D-deficient mice established the importance of NKG2D in delaying tumor development in transgenic mouse models of cancer. However, we recently demonstrated an unexpected, flip side to this coin, the ability for NKG2D to contribute to tumor growth in a model of inflammation-driven liver cancer. With a focus on the liver, here, we review current knowledge of NKG2D-mediated tumor surveillance and discuss evidence supporting a dual role for NKG2D in cancer immunity. We postulate that in certain advanced cancers, expression of ligands for NKG2D can drive cancer progression rather than rejection. We propose that the nature of the microenvironment within and surrounding tumors impacts the outcome of NKG2D activation. In a form of autoimmune attack, NKG2D promotes tissue damage, mostly in the inflamed tissue adjacent to the tumor, facilitating tumor progression while being ineffective at rejecting transformed cells in the tumor bed.

Details

Language :
English
ISSN :
16643224
Volume :
9
Database :
OpenAIRE
Journal :
Frontiers in Immunology
Accession number :
edsair.doi.dedup.....b4a8c8d0318c87344ad90c4890985816
Full Text :
https://doi.org/10.3389/fimmu.2018.01808/full