e:Med Systemmedizinischer Forschungsverbund – MelAutim – Systems medicine of melanoma and autoimmunity in the context of immunotherapy

The project MelAutim addresses the goal to uncover the molecular and cellular mechanisms involved in the interplay between cancer and autoimmunity. In particular, the focus lies on factors involved in the onset of, or the exacerbation of pre-existing autoimmune diseases during immunotherapy regimens against cancer. On this background, a model using the methods of systems biology shall be developed that enables an assessment of a patients’ individual risks before the onset of such therapies. These evaluations will support physicians’ choice of therapy and control intervals. Thereby, therapeutic targets could be identified, that without provoking conditions of autoimmunity. Ultimately, adjustment of this model in that autoimmunity is induced in silico under controlled conditions, leads to further discoveries concerning the pathology 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