The most common type of liver cancer in children, hepatoblastoma, surprisingly appears to contain many immune cells from a type that has long been overlooked.

This is according to a study by researchers at the Princess Máxima Centre and UMC Utrecht.

The discovery of these myeloid cells in liver tumours unveils new avenues for treatment.

Hepatoblastoma is the most common type of liver cancer in children.

It develops when immature liver cells remain stuck in an early stage of development and start dividing uncontrollably.

Treatment usually consists of a combination of chemotherapy and surgery to remove the tumour, and sometimes even a liver transplant is necessary.

Research into new therapies for childhood cancer therefore remains urgently needed.

Immunotherapy 

Until now, very little was known about the presence of immune cells in hepatoblastoma.

This knowledge could be a starting point for possible treatments: the right medicine could stimulate the body’s own immune cells to recognise and attack the tumour.

This approach, known as immunotherapy, is already used for various types of cancer, especially in adults.

Researchers at UMC Utrecht and the Princess Máxima Centre therefore started a research project to map the immune cells present in hepatoblastoma.

To explore whether immunotherapy could be a treatment option for children with hepatoblastoma, Yvonne Vercoulen, group leader at UMC Utrecht, and Weng Chuan Peng, group leader at the Princess Máxima Centre, started a collaboration.

Few T cells 

“Our research shows that childhood liver tumours contain few so-called T cells, immune cells that are found in tumours in adults,” says Daniëlle Krijgsman, researcher at the UMC Utrecht.

“This means we cannot treat hepatoblastomas in children with immunotherapies based on activating these T cells, which is often done in adults with cancer.”

The researchers came to this conclusion by examining biopsies, pieces of tumour tissue, of children presently or previously under treatment in the Princess Máxima Centre or the UMC Groningen, using spatial omics.

This provides a very detailed picture of the tumour.

“This technique allows us to learn much more about the types of immune cells present in the tumour,” says Krijgsman.

“We can see what kind of cells they are and exactly where they are located in the tumour.”

New treatment 

By combining the clinical expertise of the Princess Máxima Centre and the UMC Groningen with the work of both research groups, the team discovered another type of cell in children's liver tumours: so-called myeloid cells.

Like T cells, these cells can also be activated to clear other cells.

This makes them a potential target for new therapies.

In addition, the researchers observed that chemotherapy treatment might further increase the number of myeloid cells in liver tumours.

“In the future, we could therefore consider combination therapy,” says Stephanie Schubert, researcher at the Princess Máxima Centre.

“We would first treat patients with chemotherapy to direct more immune cells to the tumour, after which we could activate those cells with immunotherapy.”

Collaboration 

However, much research is still needed before a new type of therapy based on myeloid cells can be developed.

“The field of immunotherapy still focuses primarily on T cells,” says Schubert.

“Research is already underway in adults on the safety and effectiveness of immunotherapy based on myeloid cells. I think we can expect a lot in this area in the coming years.”

UMC Utrecht and the Princess Máxima Centre are working closely together to map the immune profile of childhood tumours, both teams having their own expertise – spatial omics in the team of Vercoulen, and molecular characterisation of hepatoblastoma in Peng’s team.

“It is important to know whether we can expect existing therapies to also work in childhood cancer,” says Schubert.

“And if there are differences, that provides starting points for further research into new therapies.”

This research was made possible thanks to a Boost Grant from the Cancer Research Priority Programme at UMC Utrecht, TKI-Health Holland (TumMyTOF), the Kinderen Kankervrij Foundation (KiKa), and the Kus van Kiki Foundation through the Prinses Máxima Centrum Foundation.

Utrecht Cancer: uniting expertise and innovation 

At the Utrecht Science Park, more than 1,200 researchers from UMC Utrecht, Utrecht University, Hubrecht Institute and the Princess Máxima Centre collaborate within Utrecht Cancer.

Together they accelerate progress in cancer care, research and education, aiming toimprove survival and quality of life for people and animals affected by cancer.

Article: High-plex imaging of hepatoblastoma and adjacent liver in pediatric patients reveals a predominant myeloid infiltrate expressing immune-checkpoints

Source: University Medical Center Utrecht