Role of the Immunsystem in the Pathogenesis and Diagnosis of Testicular Germ Cell Tumors

• Applicants: Dr. Fabian Alexander Gayer; Professor Dr. Holger M. Reichardt
• Subject Area: Reproductive Medicine, Urology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 534830515

Testicular germ cell cancer (TGCC) is the most common malignant tumor of young men with approximately half of them representing seminomas. This tumor entity is characterized by a prominent inflammatory infiltrate. Immune cells in the tumor microenvironment (TME) of seminomatous tumors, which in contrast to other tumor entities are considered predominantly pro-inflammatory, influence tumorigenesis and consequently the clinical outcome of patients. However, their composition in the TME and true relevance largely remain elusive up to now. Preliminary data revealed that T cell and macrophage activation occur in co-cultures of these immune cells with the seminoma cell line TCam-2, accompanied by an altered gene expression in the tumor cells. In this project, we plan to obtain deeper insights into the interactions between the immune system and the TME of seminomas. To this end, we will combine mechanistic analyses using our in vitro model with investigations based on a large number of biomaterials collected from patients. By employing a multi-omics approach, we will first identify new mediators and gene alterations. This will be followed by characterizing the communication in the TME with the help of functional assays. In addition, we will determine the role of endocrine and immunological factors influencing the TME. These experiments will be flanked by a comprehensive in vivo approach. Here we plan to analyze fresh-frozen tissue biopsies as well as sera and immune cells from the peripheral blood of TGCC patients. By characterizing soluble mediators and performing flow cytometric analyses, high throughput gene expression studies and immunohistochemistry, we will obtain a broad and detailed picture of the interactions of the local and systemic immune response with seminomatous and non-seminomatous germ cell tumors. Through complementary analyses in cell culture and of biomaterials, we expect to identify meaningful clinical-immunological predictors and achieve an extensive understanding of the role of the immunological TME for the progression of TGCC.

• DFG Programme: Research Grants