Distinct tumor ‘neighborhoods’ could guide more targeted treatments in aggressive childhood brain cancer

New research published in Nature finds that tumor cells within supratentorial ependymomas (SE)—an aggressive childhood brain cancer—cluster into distinct tumor cell populations. Much like a neighborhood, each cell subtype within these “communities” has a specific (and previously unappreciated) role to play.

Understanding how SE tumor cells form neighborhoods and the function of each cell type could help better predict how these tumor cell subtypes will respond to treatment.

Early developmental origins of tumors

The research team, led by Mariella Filbin, MD, Ph.D., Co-Director of the Brain Tumor Center at Dana Farber/Boston Children’s Cancer and Blood Disorders Center, found that each tumor is made up of different groups of cancer cells resembling very early brain cells, typically only found during the first pregnancy trimester.

These cells then develop into one of two cancer cell types: neuron-like or ependymal-like cancer cell states and types. Using single-cell and spatial transcriptomics, as well as in vitro and in vivo live-cell imaging over time, the research team mapped the patterns, niches, and functions of these different cancer cell types within the tumor.

How tumor neighborhoods are organized

They found the tumors show organized spatial patterns, shaped by factors like low-oxygen areas and mesenchymal signals, creating distinct “neighborhoods” of cell types. Tumor cells and normal cells have “favorite” cell types they communicate with, together creating a highly active tumor environment.

They also discovered that specific nearby normal brain cells can push tumor cells into highly mobile, neuron-like states, highlighting how the brain environment may influence and drive tumor spread.

While some tumor cell types mimic young neurons and their migration pattern, others behave like stem cells and only proliferate but stay stationary.

Implications for treatment and relapse

“This is the first time we have been able to assign different functions to different cancer cell types within a tumor, which might open the door for an entire new way of treating these cells,” said Filbin.

“Uncovering differences between cancer cells in the tumor helps us develop targeted therapies for each cell type. Given that each cancer cell type has a ‘job’ or ‘role’ within a tumor—e.g. some are there to proliferate, some are more mobile/invasive etc., it’s likely they will respond differently to treatment.”

Supratentorial ependymoma tumors often return after surgery and radiation therapy. Filbin and her team hope to explore whether any of the groups of cells they identified are responsible for tumor resurgence.

Other areas for future research include exploring the possibility of targeting either specific neighborhoods (e.g. the low-oxygen areas) or the interaction between tumor cells and the nearby normal brain cells.