Project description
Igniting the dialogue of cancer with the immune system
Anti-cancer therapy – whether in the form of chemotherapy, radiotherapy or immunotherapy – aims to kill cancer cells and also activate the immune system. The latter takes place as malignant cells release antigens and danger signals that trigger immune responses mainly mediated by dendritic cells. Funded by the European Research Council, the ICD-Cancer project aims to further investigate the phenomenon of immunogenic death (ICD) of cancer cells and identify strategies for inducing it. Exploitation of ICD as a therapeutic strategy is expected to stimulate tumour immunosurveillance and lead to long-lasting anti-cancer immunity.
Objective
The success of most if not all anticancer treatments depends on the (re)activation of immunosurveillance, as this has been documented for several therapeutic modalities, not only immunotherapy, but also chemotherapy, targeted therapy and radiotherapy. In response to antineoplastic drugs, malignant cells can undergo immunogenic cell death (ICD), thus exposing and releasing danger signals that act on pattern recognition receptors expressed by immune cells, in particular dendritic cells (DCs), to trigger the first steps of a therapeutically relevant anticancer immune response. Based on solid preliminary data and novel methodological approaches, we propose to obtain fundamental insights into the physicochemical properties and molecular mode of action of pharmacological ICD inducers (Objective 1), to create chemical-genetic systems for “synthetic” ICD induction for the study of ICD effects on the immune system without perturbation by pleiotropic anticancer drugs (Objective 2) and to identify new ICD-relevant immune checkpoints acting at the level of DCs (Objective 3). We will use this knowledge to generate an integrated view of the cancer-immune dialogue ignited, on one side, by malignant cells succumbing to ICD and, on the other side, DCs perceiving ICD, hence developing optimal strategies for the stimulation of tumor immunosurveillance (Objective 4). The concept of ICD has already been useful for patient-relevant biomarker discovery, drug development and trial design, strongly suggesting that a deeper exploration of this phenomenon will yield clinically relevant information.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
75006 Paris
France