Please use this identifier to cite or link to this item: https://doi.org/10.1158/0008-5472.CAN-10-1316
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. https://doi.org/10.1158/0008-5472.CAN-10-1316
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
URI: http://scholarbank.nus.edu.sg/handle/10635/126711
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-10-1316
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

82
checked on Oct 3, 2022

WEB OF SCIENCETM
Citations

82
checked on Oct 3, 2022

Page view(s)

155
checked on Oct 6, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.