New research published today in Nature finds that tumour cells within supratentorial ependymomas (SE) – an aggressive childhood brain cancer – cluster into distinct tumour cell populations.

Much like a neighbourhood in your hometown, each cell subtype within these “communities” has a specific (and previously unappreciated) role to play.

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

The research team, led by Mariella Filbin, MD, PhD, Co-Director of the Brain Tumour Centre at Dana Farber/Boston Children’s Cancer and Blood Disorders Centre, found that each tumour 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 tumour.

They found the tumours show organised spatial patterns, shaped by factors like low-oxygen areas and mesenchymal signals, creating distinct “neighbourhoods” of cell types.

Tumour cells and normal cells have “favourite” cell types they communicate with, together creating a highly active tumour environment.

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

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

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

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

Supratentorial ependymoma tumours 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 tumour resurgence.

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

Article: Multidimensional profiling of heterogeneity in supratentorial ependymomas

Source: Boston Children's Hospital