Neuroblastoma has often spread to other parts of the body at the time of diagnosis. Despite intensive treatments, such as chemotherapy and immunotherapy, the disease frequently comes back, particularly in the bone marrow. These metastases are challenging to combat because they are less responsive to conventional treatments.
Disrupted balance
In healthy bone marrow, special cells called mesenchymal stromal cells create an optimal environment for blood stem cells. These stem cells can develop into various types of blood cells: red blood cells, platelets, and immune cells. ‘In children with neuroblastoma metastases in the bone marrow, this balance is disrupted,’ explains Ilse Timmerman, postdoctoral researcher in the Tytgat group. ‘The children often suffer from anemia, and need frequent blood transfusions. Their immune system is also suppressed. We suspect that stromal cells are influenced by tumor cells, which in turn disrupt the balance in the development of stem cells into different types of immune cells.’
Searching for new targets
Timmerman aims to map out how tumor cells, stromal cells, and stem cells communicate on a molecular level. By better understanding these interactions, she hopes to develop new strategies to restore balance in the bone marrow. This would counteract immune suppression and make immunotherapy more effective at attacking tumor cells.
The approach
The research will proceed in three steps:
- Analyzing bone marrow from children with neuroblastoma, with and without bone marrow metastases, and comparing it to healthy bone marrow.
- Studying changes when tumor cells are added to bone marrow-on-a-chip, a 3D bone marrow model previously developed at Sanquin.
- Identifying key factors that can serve as targets for restoring balance in the bone marrow and testing these factors one by one in the model.
Timmerman explains: ‘We hope to discover new avenues for more effective therapies against bone marrow metastases, which could help both children with neuroblastoma and people with other tumors that metastasize to the bone marrow.’
The LSBR fellowship is a personal grant awarded to Ilse Timmerman. She will conduct the research in collaboration with Lieve Tytgat, Mirjam Belderbos, and Carlijn Voermans from Sanquin.