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

• DOI: 10.1073/pnas.1521812113
• Publication Date: 2016-03-01T04:14:31Z
• Authors: Satyendra C. Trip...; Haley L. Peters; Ayumu Taguchi; Hiroyuki Katayama; Hong Wang; Amin Momin; Mohit Kumar Jolly; Muge Celiktas; Jaime Rodriguez-C...; Hui Liu; Carmen Behrens; Ignacio I. Wistuba; Eshel Ben-Jacob; Herbert Levine; Jeffrey J. Molldrem; Samir M. Hanash; Edwin J. Ostrin
• Keywords: Feature (linguistics)

Significance The success rate of therapeutic trials that target tumor antigens is quite limited. We demonstrate for the first time to our knowledge lung cancer cells have undergone epithelial-to-mesenchymal transition lose immunoproteasome expression, resulting in markedly reduced antigen presentation. Reduced expression was associated with and can predict poor outcome non-small cell carcinoma (NSCLC) patients. Induction IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment overcome this immune escape mechanism mesenchymal by restoring functional HLA class I-bound peptides. These findings substantial relevance development effective strategies inherent resistance T cell-mediated immunotherapy.