The Paradoxical Role of NKG2D in Cancer Immunity.

Frontiers in Immunology
Sam SheppardNadia Guerra

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 transfor...Continue Reading

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Citations

Apr 23, 2019·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Mepur H RavindranathShahab Asgharzadeh
Aug 28, 2019·International Journal of Molecular Sciences·Julián Piñeiro FernándezCliona O'Farrelly
Feb 14, 2020·European Journal of Immunology·Daniela PrinzDagmar Gotthardt
Mar 31, 2019·Cancers·Lourdes GimenoJosé Antonio Campillo
Aug 28, 2020·Frontiers in Immunology·Sofie H MøllerSøren Skov
Mar 12, 2020·Oncogene·David J PinatoLorenza Rimassa
Mar 7, 2021·Cancers·Heather ArmstrongEytan Wine
Aug 7, 2021·Frontiers in Immunology·Thomas ReschKatja Kotsch

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Methods Mentioned

BETA
transgenic
super-resolution microscopy
biopsies
RNA-seq
Flow Cytometry
PCR

Software Mentioned

FlowJo
GraphPad
GraphPad Prism
Image J

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