Identifying Immune Evasion Mechanisms in Tumors Via a Genome-Wide shRNA Screen

Type of Award: Catalyst
Date Awarded: September 2013
Award End Date: August 2015
Amount Awarded: $ 199,998.00
PI(s): Thomas Gajewski, MD, PhD, UChicago; Haochu Huang, PhD, UChicago; Xiaozhong Wang, PhD, NU;

Abstract: Tumors and the host immune system interact in an intricate and dynamic manner. Many pieces of evidence suggest that the immune system can prevent tumor formation, yet tumors do occur in individuals with a competent immune system. It has long been thought that the tumor- suppressing actions of the immune system result in the selection of tumor variants that are invisible to the immune system or have acquired other mechanisms to evade or suppress immune attack. Indeed, some tumors that recur after successful immunotherapy often possess immunoresistant phenotypes. Thus it is critical to understand the mechanisms by which tumors become refractory to immune attack. We propose to study these mechanisms in a well-controlled tumor model where tumors are killed by tumor specific CD8+ T cells. We will use a genome-wide shRNA library to knock-down genes in tumor cells to screen for tumor variants that escape the immune attack. Understanding these mechanisms will help us to develop better immunotherapy for cancer.