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

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 wi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-03, Vol.113 (11), p.E1555-E1564
Main Authors: Tripathi, Satyendra C., Peters, Haley L., Taguchi, Ayumu, Katayama, Hiroyuki, Wang, Hong, Momin, Amin, Jolly, Mohit Kumar, Celiktas, Muge, Rodriguez-Canales, Jaime, Liu, Hui, Behrens, Carmen, Wistuba, Ignacio I., Ben-Jacob, Eshel, Levine, Herbert, Molldrem, Jeffrey J., Hanash, Samir M., Ostrin, Edwin J.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antigens, CD - immunology
Antigens, CD - metabolism
Biological Sciences
Cadherins - immunology
Cadherins - metabolism
Carcinoma, Non-Small-Cell Lung - immunology
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor
Cells
Disease-Free Survival
Epithelial-Mesenchymal Transition - genetics
Female
Gene Expression Regulation, Neoplastic
Genotype & phenotype
HLA Antigens - metabolism
Humans
Immune system
Lung cancer
Lung Neoplasms - immunology
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Male
Middle Aged
Peptides
PNAS Plus
Proteases
Proteasome Endopeptidase Complex - genetics
Proteasome Endopeptidase Complex - immunology
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - immunology
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - immunology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1521812113