Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

Satyendra C. Tripathi; Haley L. Peters; Ayumu Taguchi; Hiroyuki Katayama; Hong Wang; Amin Momin; Mohit Kumar Jolly; Muge Celiktas; Jaime Rodriguez-Canales; Hui Liu; Carmen Behrens; Ignacio I. Wistuba; Eshel Ben-Jacob; Herbert Levine; Jeffrey J. Molldrem; Samir M. Hanash; Edwin J. Ostrin

doi:10.1073/pnas.1521812113

Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

Satyendra C. Tripathi, Haley L. Peters, Ayumu Taguchi, Hiroyuki Katayama, Hong Wang, Amin Momin, Mohit Kumar Jolly, Muge Celiktas, Jaime Rodriguez-Canales, Hui Liu, Carmen Behrens, Ignacio I. Wistuba, Eshel Ben-Jacob, Herbert Levine, Jeffrey J. Molldrem, Samir M. Hanash, Edwin J. Ostrin

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

Abstract

The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.

Original language	English (US)
Pages (from-to)	E1555-E1564
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	11
DOIs	https://doi.org/10.1073/pnas.1521812113
State	Published - Mar 15 2016

Keywords

EMT
Immunoproteasome
Immunotherapy
NSCLC

ASJC Scopus subject areas

General

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Flow Cytometry and Cellular Imaging Facility

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10.1073/pnas.1521812113

Cite this

Tripathi, S. C., Peters, H. L., Taguchi, A., Katayama, H., Wang, H., Momin, A., Jolly, M. K., Celiktas, M., Rodriguez-Canales, J., Liu, H., Behrens, C., Wistuba, I. I., Ben-Jacob, E., Levine, H., Molldrem, J. J., Hanash, S. M., & Ostrin, E. J. (2016). Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proceedings of the National Academy of Sciences of the United States of America, 113(11), E1555-E1564. https://doi.org/10.1073/pnas.1521812113

Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. / Tripathi, Satyendra C.; Peters, Haley L.; Taguchi, Ayumu et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 11, 15.03.2016, p. E1555-E1564.

Research output: Contribution to journal › Article › peer-review

Tripathi, SC, Peters, HL, Taguchi, A, Katayama, H, Wang, H, Momin, A, Jolly, MK, Celiktas, M, Rodriguez-Canales, J, Liu, H, Behrens, C , Wistuba, II, Ben-Jacob, E, Levine, H, Molldrem, JJ , Hanash, SM & Ostrin, EJ 2016, 'Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 11, pp. E1555-E1564. https://doi.org/10.1073/pnas.1521812113

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abstract = "The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.",

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note = "Funding Information: We are thank the personnel of the University of Texas M. D. Anderson Cancer Center Sequencing Facility and Flow Cytometry and Cell Sorting Core Facility for providing assistance. Funding support was provided by the Department of Defense (DOD) Congressionally Mandated Lung Cancer Research Program, the National Cancer Institute Early Detection Program, the Canary Foundation, the Leukemia & Lymphoma Society Translational Research Program Grant (6030-12), National Institutes of Health (NIH) SPORE Grant P50 CA100632, and NIH Research Program Project Grants P01 CA049639 and P01 CA148600 (to J.J.M.). Support was also provided by NIH Training Program in Cancer Immunobiology Grant T32 CA009598 (to H.L.P.).",

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AU - Katayama, Hiroyuki

AU - Wang, Hong

AU - Momin, Amin

AU - Jolly, Mohit Kumar

AU - Celiktas, Muge

AU - Rodriguez-Canales, Jaime

AU - Liu, Hui

AU - Behrens, Carmen

AU - Wistuba, Ignacio I.

AU - Ben-Jacob, Eshel

AU - Levine, Herbert

AU - Molldrem, Jeffrey J.

AU - Hanash, Samir M.

AU - Ostrin, Edwin J.

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PY - 2016/3/15

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N2 - The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.

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Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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