Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome.
Proc Natl Acad Sci U S A
; 113(11): E1555-64, 2016 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-26929325
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Proteasome Endopeptidase Complex
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Lung Neoplasms
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2016
Type:
Article