Tumor immune evasion through IRGQ-directed autophagy

Hosts: Ian Ganley and Gopal Sapkota

Small Lecture Theatre: Medical Sciences Institute, SLS 

Abstract:  

The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumour progression. Here we show that immunity-related GTPase family Q protein (IRGQ), an uncharacterized protein to date, acts in the quality control of MHC-I molecules. IRGQ directs misfolded MHC-I towards lysosomal degradation through its unique binding mode to GABARAPL2 and LC3B. In the absence of IRGQ, free MHC-I heavy chains do not only accumulate in the cell, but are also transported to the cell surface, thereby promoting an immune response. Accordingly, mice and human patients suffering from hepatocellular carcinoma show improved survival rates with reduced IRGQ levels, due to increased reactivity of CD8+ T cells towards IRGQ knock-out tumour cells. Thus, we reveal IRGQ as a novel regulator of MHC-I quality control, mediating tumour immune evasion.  

Bio:  

Lina undertook her joint undergraduate studies in Applied Biology and Molecular Biology at the Hochschule Bonn-Rhein-Sieg (Germany) and University of Dundee (UK), respectively. For her Ph.D. research with Prof. Gopal Sapkota at the MRC Protein Phosphorylation and Ubiquitylation Unit in Dundee, Lina worked on identifying and characterising deubiquitylating enzymes regulating the TGF-beta and BMP signalling pathways. Lina was awarded the EMBO fellowship to pursue her postdoctoral research with Prof. Ivan Dikic to work on linear ubiquitylation and autophagy. Lina is currently a group leader within the Immune Signalling program at the Institute of Biochemistry II at Goethe University and her research focusses on the interplay between immune signalling and autophagy in the context of tumour progression.