Cancers are today viewed as tissues comprised by tumor and non-malignant host cells which cooperatively contribute to tumor progression, immune suppression and therapy resistance. Reprogramming of non-malignant cells, such as immune cells, is not only directed by genetic alterations in tumor cells but also mediated by the intercellular communication between host and tumor cells within the tumor microenvironment (TME). The tumor secretome mediating this communication comprises factors released by both cancer and host cells, including soluble factors and extracellular vesicles (EVs). The tumor secretome therefore holds great promise as a source of biomarkers and a target for innovative therapeutic approaches. However, the composition of the tumor secretome and the functional impact of individual components on the interaction of tumor cells and host cells remain to be investigated in detail. The Research Training Group (RTG) focuses on several tumor entities that are critically dependent on the TME such as ovarian cancer, pancreatic cancer and acute myeloid leukemia. Of particular interest is the role of NF-κB and p53-regulated secretome components, including EVs, that modulate the plasticity of tumor-associated immune cells, non-malignant bystander cells (see figure), cancer cell invasion, metastasis, and resistance to therapy. In addition, the importance of the chemotherapy-induced secretome and the ensuing DNA damage in the anti-tumor immune defense is investigated.
