Natural killer (NK) cells are sentinels within the immune system that rapidly respond to and kill diseased cells. NK cells typically target and eliminate cells lacking the surface protein MHC class I. However, many tumor cells lack this protein yet are resistant to NK cell surveillance and killing. A new study in the Journal of Clinical Investigation reveals that cytokine therapy enhances the activity of NK cells against tumors lacking MHC class I. Using murine models, David Raulet and colleagues at the University of California Berkeley determined that tumors lacking MHC class I inactivate NK cells. Mixed tumors composed of MHC class I positive and MHC class I negative cells also caused NK cell to become nonresponsive. Importantly, treatment of mice bearing MHC class I-deficient tumors with the cytokines IL-12 and IL-18 or with the H9 "superkine" restored NK cell activity, reduced tumor size, and increased survival. The results of this study support further investigation into the use of cytokine therapy for patients with tumors lacking MHC class I.
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TITLE
Cytokine therapy reverses NK cell anergy in MHC-deficient tumors
AUTHOR CONTACT:
David Raulet
University of California, Berkeley, Berkeley, CA, USA
Phone: 510-642-9521; E-mail: raulet@berkeley.edu
View this article at: http://www.jci.org/articles/view/74337?key=63d8d1b0b77cbbf366ee
ACCOMPANYING COMMENTARY TITLE:
Cytokines reinstate NK cell–mediated cancer immunosurveillance
Laurence Zitvogel
INSERM U1015, CICBT507, University Paris XI
Institut Gustave Roussy
laurence.zitvogel@gustaveroussy.fr
View this article at: http://www.jci.org/articles/view/78531?key=360e105b6bce80bf5811
Journal of Clinical Investigation