SP5 - MelAutim
Multi-level computational modelling of cancer-autoimmunity under immune-checkpoint inhibitors and other immunotherapies
The aim of the subproject is to generate a multi-level computational model describing the autoimmunity-cancer-immunotherapy axis. The model will focus in tissues with high prevalence of autoimmunity, using the joint (rheumatoid arthritis) and gut (inflammatory bowel disease) as representatives. The subproject is divided in two phases. In the first three years of the project, we will derive and characterize regulatory networks accounting for the interactions between immune cells, tissue cells and cytokines/chemokines. Furthermore, we will derive and calibrate agent-based models that have the capacity to simulate the dynamics of cells in the chosen inflammatory sites. In the final two years of the project, the agent-based models will be extended by integrating the molecular networks. This will generate a dynamic, multi-level description of the molecular mechanisms underlying the autoimmunity-cancer-immunotherapy axis. Using systematic computer simulations and data analysis techniques, the model will be used to generate in silico signatures describing the emergence or enhancement of autoimmunity under immune-checkpoint inhibitors administration.