In lung adenocarcinoma a mutation in the oncogene epidermal growth factor receptor (EGFR) is frequently found in patients. More specifically, mutations in the tyrosine kinase domain of EGFR lead to uncontrolled cell proliferation and evasion of the apoptotic pathway. To combat oncogenic EGFR signalling, different tyrosine kinase inhibitors have been developed. However, patients sustain tumor progress eventually since the tumor is developing resistance. Another important role in tumor development and progression, that has come into focus in recent years, is the tumor microenvironment. Immune checkpoint inhibitors as a therapeutic tool, such as anti-PD-1 or anti-PD-L1, overcome limited immune response and enable T-cell-mediated tumor control.
With my project I want to examine possible synergistic effects when combining targeted therapy and immunotherapy compared to monotherapies using an EGFR-L858R NSCLC mouse model. A detailed analysis of the tumor microenvironment in respective therapy cohorts will provide information about underlying mechanisms of tumor progression and immune response.