2016 Lung Cancer Research Foundation Annual Grant Program
Edwin Ostrin, MD, PhD
The University of Texas MD Anderson Cancer Center
Research Project:
The immunoproteasome -- investigating a new interaction between lung cancer and the immune system
Summary:
As lung cancer develops, it has to escape detection and elimination by the immune system. New drugs that reverse this, and allow the immune system to better attack a growing cancer, are under intense investigation. Early data shows that such treatment, termed immunotherapy, is very effective in many lung cancers.
The immunoproteasome is a cellular machine that degrades proteins into short peptide strings that a cell uses to produce a damage signal for the immune system. These damage signals are recognized by a class of immune cells that then can kill the cell with the peptide string on its surface. Lung cancer can stimulate inflammation, and early lung cancer cells use the immunoproteasome to signal to the immune system. Some lung cancers that display markers of a more aggressive behavior turn off their immunoproteasomes, display less of this damage signal, and thus evade the immune system. This proposal seeks to study the exact role of the immunoproteasome in lung cancer development and progression using animal and cell models. This work will test if treatments that turn back on the immunoproteasome in such cancers are a useful strategy that may work in concert with immunotherapy.