Understanding and Anticipating Therapeutic Response And Immuno-meDIated Adverse Events in Anti-cancer Immune-checkpoint Inhibition: a Tissue Biopsy Based imaGing Study

Immune checkpoint inhibitors (ICI) have dramatically changed the management of some types of metastatic cancer, with indications for their use continuing to expand. Despite the hope brought by these new anti-cancer molecules, the response to ICI in these poorly prognosticated cancers is heterogeneous, with a benefit observed in 20 to 30% of patients, with the combination with chemotherapy or targeted therapies offering new perspectives. By inhibiting natural checkpoints of the immune system, ICI increase the anti-tumor response, but are also responsible for immune-related adverse events (irAEs), which can be severe. There are many hypothesized mechanisms for these immune-related adverse events, but no one has ever characterized in detail the immune infiltrate within the irAEs targeted tissues. In-depth identification of cell subpopulations within the tumor microenvironment, as well as the infiltrate within the irAEs targeted tissues, would allow the identification of new predictive factors of response and toxicity, which could be used in clinical practice at the time of diagnosis. A better understanding of immuno-mediated toxicities would allow to adapt their management, which is currently based on the inflammatory diseases they mimic. The Hyperion technology is an innovative mass cytometry imaging system, allowing the simultaneous analysis of nearly 40 markers within a tissue.