In this Grand Challenge project, 4 clinical trials (breast cancer, recurrent cervical carcinoma, head-and-neck cancer and melanoma) will be initiated which involve immune checkpoint blockage therapy (here anti-PD1/PDL1 compounds) in indications of unmet clinical need. A comprehensive and unique collection of biopsies, both pre- and on-treatment, will be assembled. 

In this Grand Challenge project, the most innovative technologies, more specifically single-cell multi-omics profiling, are used for the first time in the context of clinical trials, as opposed to the ‘classical’ approach to apply bulk omics analyses. Specifically, tumor biopsies will be collected from patients receiving ICB therapy, before and during treatment as well as at disease progression. 

With this Grand Challenges project, the understanding of the molecular and cellular mechanisms underlying response and resistance to ICB therapy will be unravelled by establishing dynamic (spatial) maps of the tumor ecosystem before and during treatment. Novel predictive biomarkers will be distilled, and ultimately novel effective combination regimens will be proposed.