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Science 294 (5542): 605-609

Copyright © 2001 by the American Association for the Advancement of Science

Regulation of Cutaneous Malignancy by gamma &dgr; T Cells

Michael Girardi,1* David E. Oppenheim,2* Carrie R. Steele,2 Julia M. Lewis,1 Earl Glusac,1 Renata Filler,1 Paul Hobby,3 Brian Sutton,3 Robert E. Tigelaar,1 Adrian C. Hayday2dagger

The localization of gamma delta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gamma delta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gamma delta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

1 Department of Dermatology and Yale Skin Diseases Research Core Center,
2 Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' Medical School,
3 Randall Centre for Molecular Medicine, Guy's Hospital, King's College, London SE1 9RT, UK.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: adrian.hayday{at}kcl.ac.uk



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NKG2D ligands are expressed on stressed human airway epithelial cells.
M. T. Borchers, N. L. Harris, S. C. Wesselkamper, M. Vitucci, and D. Cosman (2006)
Am J Physiol Lung Cell Mol Physiol 291, L222-L231
   Abstract »    Full Text »    PDF »
Comparative Analysis of Regulatory and Effector T Cells in Progressively Growing versus Rejecting Tumors of Similar Origins..
J. D. Bui, R. Uppaluri, C.-S. Hsieh, and R. D. Schreiber (2006)
Cancer Res. 66, 7301-7309
   Abstract »    Full Text »    PDF »
The NKG2D-Activating Receptor Mediates Pulmonary Clearance of Pseudomonas aeruginosa.
M. T. Borchers, N. L. Harris, S. C. Wesselkamper, S. Zhang, Y. Chen, L. Young, and G. W. Lau (2006)
Infect. Immun. 74, 2578-2586
   Abstract »    Full Text »    PDF »
Conditioning of langerhans cells induced by a primary CD8 T cell response to self-antigen in vivo..
D. Mayerova, L. Wang, L. S. Bursch, and K. A. Hogquist (2006)
J. Immunol. 176, 4658-4665
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Homing and Function of Human Skin {gamma}{delta} T Cells and NK Cells: Relevance for Tumor Surveillance.
L. M. Ebert, S. Meuter, and B. Moser (2006)
J. Immunol. 176, 4331-4336
   Abstract »    Full Text »    PDF »
Placenta-Derived Soluble MHC Class I Chain-Related Molecules Down-Regulate NKG2D Receptor on Peripheral Blood Mononuclear Cells during Human Pregnancy: A Possible Novel Immune Escape Mechanism for Fetal Survival.
L. Mincheva-Nilsson, O. Nagaeva, T. Chen, U. Stendahl, J. Antsiferova, I. Mogren, J. Hernestal, and V. Baranov (2006)
J. Immunol. 176, 3585-3592
   Abstract »    Full Text »    PDF »
Proteolytic Release of Soluble UL16-Binding Protein 2 from Tumor Cells..
I. Waldhauer and A. Steinle (2006)
Cancer Res. 66, 2520-2526
   Abstract »    Full Text »    PDF »
IFN-Dependent Down-Regulation of the NKG2D Ligand H60 on Tumors.
J. D. Bui, L. N. Carayannopoulos, L. L. Lanier, W. M. Yokoyama, and R. D. Schreiber (2006)
J. Immunol. 176, 905-913
   Abstract »    Full Text »    PDF »
DNA Damage and Tumor Surveillance: One Trigger for Two Pathways.
P. Hoglund (2006)
Sci. STKE 2006, pe2
   Abstract »    Full Text »    PDF »
Cutting Edge: The AP-1 Subunit JunB Determines NK Cell-Mediated Target Cell Killing by Regulation of the NKG2D-Ligand RAE-1{epsilon}.
N. Nausch, L. Florin, B. Hartenstein, P. Angel, M. Schorpp-Kistner, and A. Cerwenka (2006)
J. Immunol. 176, 7-11
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Cancer Cells Become Susceptible to Natural Killer Cell Killing after Exposure to Histone Deacetylase Inhibitors Due to Glycogen Synthase Kinase-3-Dependent Expression of MHC Class I-Related Chain A and B.
S. Skov, M. T. Pedersen, L. Andresen, P. Thor Straten, A. Woetmann, and N. Odum (2005)
Cancer Res. 65, 11136-11145
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The Biology of {gamma}{delta} T Cells: What Is the Relationship between {gamma}{delta} T Cells and Cancer? Will an Increased Number and/or Function of {gamma}{delta} T Cells Result in Lower Cancer Incidence?.
W. L. Havran (2005)
J. Nutr. 135, 2909S
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JNK1 Is Essential for CD8+ T Cell-Mediated Tumor Immune Surveillance.
Y. Gao, J. Tao, M. O. Li, D. Zhang, H. Chi, O. Henegariu, S. M. Kaech, R. J. Davis, R. A. Flavell, and Z. Yin (2005)
J. Immunol. 175, 5783-5789
   Abstract »    Full Text »    PDF »

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