High-grade gliomas are fast-growing brain tumors in children. The prognosis for these children is often dismal. Current treatments are limited, and immunotherapy, a form of treatment that uses the body's own immune system to fight cancer, has so far yielded few results. Researchers from the Van Vuurden and Rios group have uncovered an important cause for this: the tumor environment actively suppresses the immune system.
New techniques reveal immune landscape
The researchers used new imaging techniques to analyze the tumor tissue of 32 children who are being treated or have been treated at the Máxima. Thijs van den Broek, PhD candidate in the Van Vuurden group and Rios group, explains: 'In our analyses, we used cyclic immunofluorescence and spatial transcriptomics, among other techniques. This enabled us to discover that the immune environment of these tumors consists mainly of so-called myeloid cells. The T cells, which are essential for attacking cancer cells, were scarce.'
Within the myeloid cells, the researchers found a specific type of cell, recognizable by two proteins: SPP1 and GPNMB. These cells gather around specific tumor cells and are located further away from T cells. They also activate genes that suppress the immune system and help the surrounding tissue adapt to the tumor. 'In this way, they create an environment that protects the tumor from immune cells and, in part, stimulates its growth,' said van den Broek.
New starting points for therapy
By examining how different cells interact with the tumor, the research provides important new insights. 'The cells found are a promising new starting point for immunotherapy in children with high-grade gliomas . By targeting this subtype of myeloid cells, we may be able to strengthen the immune response and improve the prognosis for children with this type of cancer,' says Dr. Dannis van Vuurden, a pediatric oncologist specializing in the treatment of brain tumors and research group leader.
Next steps
The researchers are now investigating how the interactions between these immune cells and the tumor cells can be blocked. This could potentially be used as a new immunotherapy or make existing immunotherapies more effective.
The results were published today in the journal Neuro-Oncology Pediatrics. The research was made possible in part by project funding from Stichting Kinderen Kankervrij (KiKa) and Fight Kids Cancer.