Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome
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- Satyendra C. Tripathi
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Haley L. Peters
- Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Ayumu Taguchi
- Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Hiroyuki Katayama
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Hong Wang
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Amin Momin
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Mohit Kumar Jolly
- Center for Theoretical Biological Physics, Rice University, Houston, TX;
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- Muge Celiktas
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Jaime Rodriguez-Canales
- Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Hui Liu
- Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Carmen Behrens
- Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Ignacio I. Wistuba
- Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Eshel Ben-Jacob
- Center for Theoretical Biological Physics, Rice University, Houston, TX;
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- Herbert Levine
- Center for Theoretical Biological Physics, Rice University, Houston, TX;
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- Jeffrey J. Molldrem
- Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Samir M. Hanash
- Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
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- Edwin J. Ostrin
- Department of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
書誌事項
- 公開日
- 2016-02-29
- 権利情報
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- http://www.pnas.org/preview_site/misc/userlicense.xhtml
- DOI
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- 10.1073/pnas.1521812113
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>The success rate of therapeutic trials that target tumor antigens is quite limited. We demonstrate for the first time to our knowledge that lung cancer cells that have undergone epithelial-to-mesenchymal transition lose immunoproteasome expression, resulting in markedly reduced antigen presentation. Reduced expression of the immunoproteasome was associated with and can predict poor outcome in non-small cell lung carcinoma (NSCLC) patients. Induction of the immunoproteasome with IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment can overcome this immune escape mechanism of mesenchymal cells by restoring functional HLA class I-bound peptides. These findings have substantial relevance for development of effective strategies to target tumor cells with inherent resistance to T cell-mediated immunotherapy.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 113 (11), E1555-, 2016-02-29
Proceedings of the National Academy of Sciences