Our Interest
Immune checkpoint inhibition (CKI) has demonstrated remarkable efficacy in several types of cancer, representing a major breakthrough in cancer therapy. These therapies are unique in that the primary target is not the tumor cell itself, but the crosstalk between immune cells and cancer cells within the tumor microenvironment.
Immune checkpoint inhibition (CKI) has demonstrated remarkable efficacy in several types of cancer, representing a major breakthrough in cancer therapy. These therapies are unique in that the primary target is not the tumor cell itself, but the crosstalk between immune cells and cancer cells within the tumor microenvironment.
We have described a negative prognostic impact of PD-L1 expression on tumor cells in esophagogastric adenocarcinoma (EGA), and CKI has been approved as both adjuvant and palliative treatment. Despite these promising results, only a minority of patients respond to CKI monotherapy, and the mechanisms underlying resistance remain poorly understood.
Successful recognition of tumor cells by immune cells is crucial for the therapeutic efficacy of CKI. This recognition depends on a broad spectrum of immune-related, tumor cell–intrinsic and –extrinsic factors and can currently only be partially predicted by surrogate markers (e.g., mutational burden). Therefore, multidimensional analyses of tumor immunogenicity—including immune infiltration, private and shared neoantigens, tumor-specific immune responses, and mechanisms of immune escape—are essential to further improve therapeutic efficacy and translational research in this field.
One key project of our group focuses on tumor-specific endogenous immune responses in EGA. Closely related to this project, we are conducting a clinical trial evaluating the addition of CKI to neoadjuvant treatment of EGA. Our second main research interest is the impact of tumor-specific B-cell responses on tumor immunogenicity. Overall, we aim to further elucidate immune escape as a key mechanism of primary and secondary resistance to immune checkpoint inhibition.
Translational Relevance
Our research has immediate translational relevance, as the endogenous immune response is likely the most important factor determining the success or failure of emerging immunotherapies. Taken together, our analyses aim to contribute to the implementation of immunotherapy into treatment algorithms for gastrointestinal cancers, improve translational analyses, and support the tailored design of future clinical trials. These insights may be of similar relevance to cancers of different origins.
Our research has immediate translational relevance, as the endogenous immune response is likely the most important factor determining the success or failure of emerging immunotherapies. Taken together, our analyses aim to contribute to the implementation of immunotherapy into treatment algorithms for gastrointestinal cancers, improve translational analyses, and support the tailored design of future clinical trials. These insights may be of similar relevance to cancers of different origins.
Where to find us