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2. RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R, Bert, Nina Le, Ho, Samantha Sw, Shen, Yu J, Tang, Li Fm, Xiong, Gordon M, Croxford, John L, Koo, Christine X, Ishii, Ken J, Akira, Shizuo, Raulet, David H, and Gasser, Stephan

Subjects
Genetics, Biotechnology, Cancer, Rare Diseases, Lymphoma, Hematology, Aetiology, 2.1 Biological and endogenous factors, Animals, Cell Line, Tumor, DNA Damage, DNA, Neoplasm, Immunologic Surveillance, Interferon Regulatory Factor-3, Killer Cells, Natural, Ligands, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, NK Cell Lectin-Like Receptor Subfamily K, Nuclear Matrix-Associated Proteins, Nucleocytoplasmic Transport Proteins, Phosphorylation, Protein Serine-Threonine Kinases, Transfection, Up-Regulation, Protein-Serine-Threonine Kinases, Oncology and Carcinogenesis, Oncology & Carcinogenesis
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.

Published
2014

3. Supplementary Figure Legends from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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4. Supplementary Figure 6 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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5. Supplementary Figure 3 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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6. Supplementary Figure 5 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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8. Supplementary Figure 2 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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9. Supplementary Figure 4 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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10. Supplementary Figure 7 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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11. Supplementary Figure 1 from RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

Author

Lam, Adeline R., primary, Le Bert, Nina, primary, Ho, Samantha S.W., primary, Shen, Yu J., primary, Tang, Melissa L.F., primary, Xiong, Gordon M., primary, Croxford, J. Ludovic, primary, Koo, Christine X., primary, Ishii, Ken J., primary, Akira, Shizuo, primary, Raulet, David H., primary, and Gasser, Stephan, primary

Published
2023
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