Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 29, 2016
- Source ID
- 10.1073/pnas.1521812113
Entities
People
- Amin Momin
- Ayumu Taguchi
- Carmen Behrens
- Edwin J. Ostrin
- Eshel Ben-jacob
- Haley L. Peters
- Herbert Levine
- Hiroyuki Katayama
- Hong Wang
- Hui Liu
- Ignacio I. Wistuba
- Jaime Rodriguez-canales
- Jeffrey J. Molldrem
- Mohit Kumar Jolly
- Müge Çeliktaş
- Samir M Hanash
- Satyendra C. Tripathi
Organizations
- Cancer Prevention and Research Institute of Texas
- Leukemia & Lymphoma Society
- National Cancer Institute
- National Institutes of Health
- Rice University
- United States Department of Defense
- University of Texas at Austin