Schlößer, Hans A - B 09

Despite modern multimodality therapies, the overall prognosis of esophagogastric adenocarcinoma (EGA) remains poor. Addition of immunotherapy targeting PD-(L)1 has been approved in different clinical settings. However, more than 70% of patients did not benefit from anti-PD-1 monotherapies and mechanisms underlying resistance are poorly understood. We are investigating genomic, epigenetic and immune related aspects associated with immunogenicity of EGA in patient-derived material. Additionally, we use cutting-edge stomach-specific (Anxa10 promotor) genetically engineered orthotopic mouse models resembling two major genomic subtypes of EGA. The immune microenvironments of these models reflect human EGA and both mouse models are resistant to anti-PD1 monotherapy. 

This project aims to explore defective antigen presentation and especially alterations of the IFN-y pathway as promising targets for combined immunotherapies of EGA. Overcoming immunotherapy-resistance in our preclinical models is the main goal of our project.

We completed a prospective clinical trial evaluating addition of anti-PD-L1 therapy to standard neoadjuvant chemo-radiotherapy of EGA. The proposed in-vivo experiments are complementary to this unique source of EGA samples treated with immunotherapy. As we can build on an established translational immune-monitoring platform and a successfully completed clinical trial, demonstration of in-vivo efficacy of combined immunotherapies would significantly support translation into a clinical trial.

For more information please check Schlößer Lab. 

• Center for Molecular Medicine Cologne (CMMC)
• Dept. of General, Visceral, Tumor and Transplantation Surgery