The MelAutim project aims to uncover the molecular and cellular mechanisms for the interaction of cancer and autoimmunity, in particular with regard to factors involved in the development or aggravation of pre-existing autoimmune diseases during immunotherapy. Based on this understanding, a model shall be developed using methods of systems medicine, which will help to assess the individual patient’s risk even before the start of therapy and thus support physicians in the selection of therapy and control intervals. On the one hand, this could help to identify therapeutic targets that induce an antitumoral response without inducing autoimmunity. On the other hand, the investigation of this model, in which autoimmunity is triggered under controlled conditions, could provide insights into the pathomechanisms of autoimmune diseases.
Subproject 1 (SP1): Targeting the crosstalk between melanoma and immune cells by reprogramming the cancer secretome
The IEGT subproject investigates how melanoma cells influence immune cells through their secretome, achieving disease progression, immunotherapy resistance and flares of pre-existing autoimmune diseases. The focus will be on the immunomodulatory properties of the melanoma secretome upon upregulation of E2F1 transcription factor in tumor cells. We intend to unveil E2F1/cofactor/gene axes which reprogram the secretome towards supporting tumor progression and deregulating immune responses. Using systems pharmacology-based approaches, molecular therapeutics capable of reversing the currently poor clinical outcome will be developed and tested in mouse models.
This project is funded by the Federal Ministry of Education and Research (BMBF) 01ZX1905D, DLR Projektträger– Gesundheit