In bad company: Immune cells in the tumor environment determine the success of treatment for childhood brain tumors

The “Hopp Children's Cancer Center Heidelberg” (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and Heidelberg University (Uni HD).

Low-grade gliomas are the most common type of tumor in children and at the same time have been little studied. The tumors are usually benign and young patients generally have a good survival rate. In many cases, however, the tumors continue to grow, neurological impairments occur and the children have to struggle with the effects of the tumors and the treatment for the rest of their lives.

Why some tumors grow quickly or slowly, are easier or harder to control and in some cases relapse despite successful treatment depends not only on the cancer cells themselves, but also on the cells in the surrounding area. The tumor uses various tricks to manipulate the cells in the vicinity so that they form blood and lymph vessels that supply it, support the tumor tissue or even influence the blood-brain barrier so that drugs cannot penetrate. At the same time, immune cells migrate in, suppressing the immune system and protecting the tumor from attacks by other immune cells.

“This is highly complex and it was previously difficult to analyze the exact composition of the tumor microenvironment in childhood low-grade gliomas in order to be able to make predictions about the course of therapy, for example,” explains Till Milde from the Hopp Children's Cancer Center Heidelberg (KiTZ) and Heidelberg University Hospital (UKHD), who has been head of the Department of Pediatric and Adolescent Medicine at Jena University Hospital since this year.

Together with Romain Sigaud from the Hopp Children's Cancer Center Heidelberg (KiTZ), Jena University Hospital and the German Cancer Research Center (DKFZ) and other colleagues, including from McGill University, Montreal, Canada, the research team has now succeeded in characterizing the “immune cell profile” of the tumor environment, which could also be used as a marker for prognosis in the future. The research team analyzed 120 tumor samples from children and adolescents using a comparatively new method, imaging mass cytometry. High-resolution microscopic imaging is combined with mass spectrometry to visualize many proteins in tissue samples with high spatial resolution.

A striking common feature in the tumor environment of the samples examined was the large number of so-called myeloid cells, a group of immune cells. The protein composition of these myeloid cells also suggests that they suppress the immune defense in the tumor and that it is therefore not attacked by the body's own defenses. Children with a relapse showed a particularly characteristic “immune cell profile” in the tumor environment, which could be used as a marker to identify high-risk patients in the future.  The composition of the tumor environment also varied depending on the brain region in which the tumor had occurred

In addition, the researchers also found particularly high concentrations of a certain receptor in the myeloid cells of the tumor environment, which is responsible for the communication of the cancer cells with the cells in their environment, as previous studies suggest. 
“This is good news, because there are already clinical studies in which patients with solid tumors respond well to the blockade of this receptor,” says Till Milde. “We therefore hope that this therapy could also help children and adolescents with low-grade glioma and that we can use the results of our work to develop further approaches to positively influence the tumor microenvironment.”

 

Original publication:
A. F. Andrade et al. Revealing MAPK-Activated Immune-Suppressive Myeloid Populations in Pediatric Low-1 Grade Gliomas Through Spatial Immune Mapping. Nature Immunology (Online publication, September 12, 2025) DOI: 10.1038/s41590-025-02268-7