2. Academic Validation
  3. Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

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. 2016 Mar 15;113(11):E1555-64. doi: 10.1073/pnas.1521812113.
Satyendra C Tripathi 1,  Haley L Peters 2,  Ayumu Taguchi 3,  Hiroyuki Katayama 1,  Hong Wang 1,  Amin Momin 1,  Mohit Kumar Jolly 4,  Muge Celiktas 1,  Jaime Rodriguez-Canales 3,  Hui Liu 3,  Carmen Behrens 3,  Ignacio I Wistuba 3,  Eshel Ben-Jacob 4,  Herbert Levine 5,  Jeffrey J Molldrem 2,  Samir M Hanash 1,  Edwin J Ostrin 6
Affiliations

Affiliations

  • 1 Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
  • 2 Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
  • 3 Department of Translational Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
  • 4 Center for Theoretical Biological Physics, Rice University, Houston, TX;
  • 5 Center for Theoretical Biological Physics, Rice University, Houston, TX; herbert.levine@rice.edu EJOstrin@mdanderson.org.
  • 6 Department of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 herbert.levine@rice.edu EJOstrin@mdanderson.org.
PMID: 26929325 DOI: 10.1073/pnas.1521812113
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.

Keywords

EMT; NSCLC; immunoproteasome; immunotherapy.

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