Cytokines reinstate NK cell–mediated cancer immunosurveillance
Laurence Zitvogel, Guido Kroemer
Laurence Zitvogel, Guido Kroemer
Published October 20, 2014
Citation Information: J Clin Invest. 2014;124(11):4687-4689. https://doi.org/10.1172/JCI78531.
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Commentary

Cytokines reinstate NK cell–mediated cancer immunosurveillance

Abstract

In healthy individuals, cells that lose expression of MHC class I molecules are quickly targeted for elimination by NK lymphocytes. A paradox in cancer immunology is the observation that many tumor cells often have a drastic reduction of MHC class I molecules, yet these cells are not eliminated by NK cells, as they should be. In this issue of the JCI, Ardolino et al. demonstrate that NK cells that infiltrate MHC class I–deficient tumors acquire an anergic state that can be reversed by particular combinations of exogenous cytokines. These results indicate that IL-12 plus IL-18 or a recombinant interleukin engineered to stimulate the IL-2 receptor β/γ heterodimer (but not the IL-2 receptor α/β/γ complex) have the potential to be used clinically to reinstate immunosurveillance against MHC class I–deficient tumors.

Authors

Laurence Zitvogel, Guido Kroemer

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Figure 1

Restoring intratumoral NK cell functions with cytokines.

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Restoring intratumoral NK cell functions with cytokines. When tumor cell...
When tumor cells lose MHC class I expression, which can occur for a variety of reasons, they disarm the function of NK cells, which become “unlicensed.” However, upon administration of the combination of IL-12 plus IL-18 or H9, NK cells regain their functions, including phosphorylation of the stress kinase ERK1/2, production of granzyme B, and secretion of IFN-γ, and recover their capacity to control tumor progression.