Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma.

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Title Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma.
Author Vider, Jelena
Journal Name Journal of Immunology
Year Published 2003
Place of publication USA
Publisher American Association of Immunologists
Abstract Evasion of host immune responses is well documented for viruses and may also occur during tumor immunosurveillance. The mechanisms involve alterations in MHC class I expression, Ag processing and presentation, chemokine and cytokine production, and lymphocyte receptor expression. Epithelial tumors overexpress MHC class I chain-related (MIC) molecules, which are ligands for the activating receptor NKG2D on NK and T cells. We report that NK cells from patients with colorectal cancer lack expression of activating NKG2D and chemokine CXCR1 receptors, both of which are internalized. Serum levels of soluble MIC (sMIC) are elevated and are responsible for down-modulation of NKG2D and CXCR1. In contrast, high serum levels of CXC ligands, IL-8, and epithelial-neutrophil-activating peptide (ENA-78) do not down-modulate CXCR1. In vitro, internalization of NKG2D and CXCR1 occurs within 4 and 24 h, respectively, of incubating normal NK cells with sMIC-containing serum. Furthermore, natural cytotoxicity receptor NKp44 and chemokine receptor CCR7 are also down-modulated in IL-2-activated NK cells cocultured in MIC-containing serum-an effect secondary to the down-modulation of NKG2D and not directly caused by physical association with sMIC. The patients' NK cells up-regulate expression of NKG2D, NKp44, CXCR1, and CCR7 when cultured in normal serum or anti-MIC Ab-treated autologous serum. NKG2D(+) but not NKG2D(-) NK cells are tumoricidal in vitro, and in vivo they selectively traffic to the xenografted carcinoma, form immunological synapse with tumor cells, and significantly retard tumor growth in the SCID mice. These results suggest that circulating sMIC in the cancer patients deactivates NK immunity by down-modulating important activating and chemokine receptors.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.jimmunol.org/content/171/12/6891
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Volume 171
Issue Number 12
Page from 6891
Page to 6899
ISSN 0022-1767
Date Accessioned 2012-04-11; 2012-07-12T23:14:43Z
Research Centre Heart Foundation Research Centre; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Cancer Therapy (excl Chemotherapy and Radiation Therapy)
URI http://hdl.handle.net/10072/45827
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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