Event Title : Understanding the regulation of constitutive and immunoproteasome expression in human cancers

Session Theme :Signalling to regulation, Session Chair : Sonia Sen
Speaker Name: 
Rahul Kumar
Start Time: 
Tuesday, January 11, 2022 - 19:00
End Time: 
Tuesday, January 11, 2022 - 19:10
Talks Abstract: 

Recent studies have shown that the expression of Immunoproteasome genes (PSMB8/9) is associated with a better prognosis in melanoma and breast cancer patients. However, the impact of the relative expression levels of both constitutive and immunoproteasomes, and their regulators, across tumor types is not well understood. In this study, by using TCGA data covering 33 tumor types, we find that the expression of constitutive and immunoproteasome is positively correlated in multiple tumor types. However, the relative expression of the constitutive is higher than the immunoproteasome. Furthermore, by using single-cell gene expression data from breast and colon tumors, we show that the immunoproteasomes are expressed not only in immune cells that are infiltrating the tumors but also in the epithelial tumor cells. In addition, the expression of both constitutive and immunoproteasomes are relatively higher in epithelial tumor cells that are close to the tumor border than the core region. Besides, the upregulation of interferon-gamma, interferon-alpha and inflammatory pathways in tumor cells, and cytotoxic immune cells infiltration, are positively correlated with the immunoproteasome expression in multiple tumor types. In contrast, the negative regulators of immunoproteasome expression (such as EMT and WNT signalling) are tissue and tumor type specific. We also developed a model to show that immunoproteasome in combination with other cellular factors is a better predictor of patient survival.

Event Day: 
Day 2 (11th Jan 2022)