Abstract A060: Immunoproteasome deficiency is a feature of NSCLC with a mesenchymal phenotype and is associated with restricted antigen presentation and poor outcome in patients

Proteasomes are multi-subunit complexes that degrade intracellular proteins through the ubiquitin-proteasome pathway. The immunoproteasome generates peptides that are particularly suitable for binding onto HLA I molecules, thus facilitating antigen presentation leading to CD8+ T cell responses. Lack of expression or down regulation of the immunoproteasome may contribute to immune evasion through antigen loss. The expression of the immunoproteasome and its impact on antigen presentation in tumors of epithelial origin is not well established. Here, we have investigated the constitutive and induced expression patterns of immunoproteasome subunits in lung cancer and their consequence on antigen presentation. We have also assessed the impact of immunoproteasome expression on prognosis for non-small cell lung carcinoma (NSCLC) patients. Proteomic profiling of the immunoproteasome in 42 NSCLC cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. We observed highly variable immunoproteasome expression among NSCLC cell lines and tumor tissues. Immunohistochemistry data revealed loss of immunoproteasome subunit is significantly correlated with loss of E-cadherin and expression of N-cadherin in NSCLC tumors. Loss of immunoproteasome subunits was also significantly associated with advanced stage (p = 0.014), recurrence (p = 0.02) and metastasis (p Citation Format: Satyendra C. Tripathi, Haley L. Peters, Edwin J. Ostrin, Ayumu Taguchi, Hiroyuki Katayama, Hong Wang, Amin Momin, Mohit K. Jolly, Muge Celiktas, Jaime Rodriguez, Carmen Behrens, Ignacio I. Wistuba, Eshel Ben Jacob, Herbert Levine, Jeffrey J. Molldrem, Samir M. Hanash. Immunoproteasome deficiency is a feature of NSCLC with a mesenchymal phenotype and is associated with restricted antigen presentation and poor outcome in patients. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A060.