A team of researchers discovered that reduced expression of the immunoproteasome is associated with poor clinical outcome in patients with non-small-cell lung carcinoma.
Researchers analyzed data gathered over the years and found that patients with early stage non-small-cell lung cancer — the most common type — who have low levels of immunoproteasome expression are more likely to have recurrent and metastatic cancers. Moreover, the team found that this low expression is associated with transition from epithelial-type cells, which bind to each other to form skin and organ linings, to free-floating mesenchymal-type cells, which are known to be more resistant to chemotherapy and immunotherapy treatments.
The research team also profiled protein expression in different cancer cell lines and correlated it to patient outcome, developing computer models that allowed them to rapidly combine and evaluate protein-signaling pathways as the disease progressed.
“The idea was to leave no stone unturned. We modeled the changes in gene expression that can be readily measured, how they might be caused, and how these are correlated to all the other changes going on in the cells,” Dr Herbert Levine, the study’s co-author, said in a press release. “We want to go from the basic biology of defining the circuits and how they change the expression of these key proteins to showing that they really do have a consequence in terms of recognition by the immune system.”
From all the studies, researchers concluded that immunoproteasome suppression is a consequence of feedback loops activated by the transition to mesenchymal-type cells. Importantly, researchers achieved induction of the immunoproteasome with IFN? or 5-aza-2?-deoxycytidine (5-aza-dC) treatment — results that may have substantial relevance to the development of effective strategies to target tumor cells with inherent resistance to T-cell-mediated immunotherapy.