SP2A - MelAutim

Role of macrophages during checkpoint-controlled autoimmunity and immune-therapy

The overall goal of this subproject is to detect and understand molecular pathways that trigger inflammation and autoimmunity in response to cancer immunotherapies such as immune checkpoint inhibitors. We plan to determine the contribution of on the role of mononuclear phagocytes (including monocytes and macrophages) to the anti-tumor immune response and autoimmune-triggered inflammation, respectively. To this end, we will generate single-cell RNA sequencing of mononuclear phagocytes isolated from draining lymph nodes and tumors. Using network analysis, the data will be used in SP4 and SP5 to determine computationally molecular pathways and cell-to-cell interaction mechanisms pivotal in the activation of monocytes and macrophages during checkpoint therapy-induced autoimmunity and anti-tumour immune response, insights that later will be experimentally validated in this subproject through in vitro experiments and mouse models.