In C02 G. Herter-Sprie and C. Reinhardt will employ a next generation genetically engineered mouse model to analyze the role of genomic instability on SCLC immunogenicity and thereby immune surveillance, identify whether radiation and chemotherapy influence the sensitivity towards immunological modulation, and characterize the anti-tumor efficacy of PD-1:PD-L1-blocking antibodies, upon prior regulatory T cells (T_Reg) repression. Ultimately, the findings from this project will help clinicians to design informed patient-tailored clinical studies.