Abstract:
:The immunoreceptor NKG2D originally identified in natural killer (NK) cells recognizes ligands that are upregulated on tumor cells. Expression of NKG2D ligands (NKG2DL) is induced by the DNA damage response (DDR), which is often activated constitutively in cancer cells, revealing them to NK cells as a mechanism of immunosurveillance. Here, we report that the induction of retinoic acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING-dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3. Cytosolic DNA was detected in lymphoma cell lines that express RAE1 and its occurrence required activation of the DDR. Transfection of DNA into ligand-negative cells was sufficient to induce RAE1 expression. Irf3(+/-);Eμ-Myc mice expressed lower levels of RAE1 on tumor cells and showed a reduced survival rate compared with Irf3(+/+);Eμ-Myc mice. Taken together, our results suggest that genomic damage in tumor cells leads to activation of STING-dependent DNA sensor pathways, thereby activating RAE1 and enabling tumor immunosurveillance.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lam AR,Bert NL,Ho SS,Shen YJ,Tang LF,Xiong GM,Croxford JL,Koo CX,Ishii KJ,Akira S,Raulet DH,Gasser Sdoi
10.1158/0008-5472.CAN-13-1703subject
Has Abstractpub_date
2014-04-15 00:00:00pages
2193-2203issue
8eissn
0008-5472issn
1538-7445journal_volume
74pub_type
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