Elisa Zappa - Immune interventions from scRNAseq analysis from debulked neuroblastoma tumours
PhD project 1: neuroblastoma
|Institute:||Princess Máxima Center for Pediatric Oncology|
|Supervisor:||Dr. Jan Molenaar|
|Co-Supervisors:||Dr. Gudrun Schleiermacher and Dr. Esther Drent|
|Doctoral Program:||Cancer Stem Cells & Developmental Biology|
|Secondments:||Institute Curie (France) and Gadeta B.V. (Netherlands)|
Neuroblastoma (NB) are heavily pre-treated using 6 courses of high dose chemotherapy. The remaining tumour is then surgically removed (debulking of tumour). After stem cell transfusion and maintenance therapy using anti GD2 most patients go into a clinical remission. But in due time most of these patients relapse. We hypothesize that debulked tumour materials still contain living tumour cells and that these cells are causing relapses. We will study the debulked tumour to type the tumour cells that cause relapses and to type the tumour microenvironment to identify new immunologic interventions.
We expect to type the tumour microenvironment in 20 debulked NB samples using scRNAseq. This will give information on the phenotype of the cells that survive heavy pre-treatment and that will eventually cause relapse formation. We expect to type the processes that prevent the T-cells from proper functioning. We expect to have TIL’s and organoids available from 10 patients. We will use these data to identify two immune based intervention that we will test in our co-culture systems. Eventually aim to prioritize one therapeutic intervention for clinical implementation.