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Title: Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition
Authors: Fine, J.H.
Chen, P.
Mesci, A.
Allan, D.S.J.
Gasser, S. 
Raulet, D.H.
Carlyle, J.R.
Issue Date: 15-Sep-2010
Citation: Fine, J.H., Chen, P., Mesci, A., Allan, D.S.J., Gasser, S., Raulet, D.H., Carlyle, J.R. (2010-09-15). Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition. Cancer Research 70 (18) : 7102-7113. ScholarBank@NUS Repository.
Abstract: Natural killer (NK) cells can recognize and kill tumor cells lacking "self" markers, such as class I MHC, but the basis for this recognition is not completely understood. NKR-P1 receptors are members of the C-type lectin-related NK receptor superfamily that are conserved from rodents to humans. Identification of Clr ligands for the NKR-P1 receptors has facilitated functional analysis of MHC-independent target cell recognition by NK cells. One receptor-ligand pair, NKR-P1B:Clr-b, can mediate "missing-self" recognition of tumor and infected cells, but the role of this axis in sensing stressed cells remains unknown. Here, we show that Clr-b is rapidly downregulated in cells undergoing genotoxic and cellular stress at the level of both RNA and surface protein. Stress-mediated loss of Clr-b on leukemia cells enhanced cytotoxicity mediated by NKR-P1B+ NK cells. Notably, Clr-b downregulation was coordinated functionally with stress-mediated upregulation of NKG2D ligands (but not class I MHC). Our findings highlight a unique role for the MHC-independent NKR-P1B:Clr-b missing-self axis in recognition of stressed cells, and provide evidence of two independent levels of Clr-b regulation in stressed cells. ©2010 AACR.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-10-1316
Appears in Collections:Staff Publications

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