The landscape of a tumour is diverse. Nestled among the frantically dividing cells are immune cells, newly-formed blood vessels, and a class of suspiciously quiet cancer cells that can have devastating effects. These dormant, or ‘quiescent’, cells can evade treatment and subsequently lead to cancer spread or resurgence. Researchers at the LMS, Imperial and UCL are hunting these cells, asking where they sit within untreated tumours, what characterises them, and what surrounds them. The team have used publicly-available data to create a map of breast cancer tumours, and found distinct pockets of quiescent cells, surrounded by cells that may act as a protective guard.

Silent but deadly

“Quiescent cancer cells are very dangerous,” explains Dr Alexis Barr, co-lead author and head of the Cell Cycle Control group at the LMS. “These cells can hide from chemotherapy and then remain in this dormant quiescent state in the tumour, and then later reactivate to drive proliferation.”

Some cancer cells take up this state, essentially pausing their progress, in response to the stress of tumour life, where nutrients and blood flow can take time to keep up with rapid tumour expansion. Like a bear hibernating through harsh conditions, they wait until more favourable conditions return, potentially after any treatment is finished. Alexis adds, “If we want to achieve long term control of peoples’ tumours and prevent tumour relapse, we have to focus on these dormant quiescent cancer cells, and have to understand more about them.”

To do this, Alexis worked with Dr Maria Secrier’s computational biology team at UCL to establish a detailed map of the tumour and its surrounding immune and support cells. They combined single-cell RNA sequencing, which showed which genes individual cells were using, with spatial transcriptomics, which then mapped the cells and their neighbours within the tumour.

“We found cells that resemble therapy-resistant cells already residing in the tumour before we give any treatment,” says Maria, which suggests that features linked to treatment resistance can be built into the tumour rather than only developing in response to treatment. This was the case both in aggressive tumour types and slower-developing classes – a surprising finding because quiescence had previously been associated with slower-growing disease.

Gated communities

The team’s tumour analysis didn’t just map cancer cells, but also the wide variety of support cells that are drawn into tumour growth. And they found a repeating pattern: dormant cells were commonly found near CXCL10-positive macrophages (a type of immune cell) and myofibroblastic cancer-associated fibroblasts (a type of tumour-supporting cell). These cells appear to have been co-opted to protect the cells, possibly forming a barrier to keep cancer-killing immune cells or cancer treatments from disturbing the sleepy neighbourhood.

“The cancer cells are really encapsulated within these areas of macrophages and fibroblasts that we think act as shields for these dormant cancer cells,” said Maria. “But we don’t yet know the direction of cause and effect: whether the surrounding cells push cancer cells into dormancy or if the cancer cells attract or alter their surroundings. It’s very likely coming from both sides.”

Treating every part of a tumour

Many chemotherapy drugs are most effective against rapidly dividing cells. But as any teacher knows, you can’t ignore the quiet ones. This study suggests proliferating and dormant regions may have different drug sensitivities. The analysis found increased activity of the complement pathway (a part of the immune system) within dormant niches, which may make these regions vulnerable to treatments targeting this pathway. The surrounding support cells may provide another potential target, although their role in maintaining dormancy still needs to be tested.

“Different parts of the tumour will likely respond to different drugs,” said Maria. “If we understand what drug combinations we can use to target both the proliferative and the dormant areas, potentially that could be more successful than current therapies. This is giving us a first insight into how we can then intervene with different therapeutics that specifically target different areas of the tumour where the cells have adapted and have evolved differently.”

Alexis said, “It is clearly important to focus on proliferative cancer cells, but we also need to understand this population of quiescent dormant cancer cells. And that’s been less studied.”

The predictions of this research will now need to be tested experimentally, but identifying in-built treatment-resistant regions in tumours and deciphering their support systems may ultimately offer a way to design more effective treatment combinations. Putting quiescent cells on the map will lead towards better cancer treatments that last.

This work was primarily funded by a UKRI Future Leaders Fellowship, the Medical Research Council and the Biotechnology and Biological Sciences Research Council.

This article was written by Anthony Lewis, Freelance Science Multimedia Producer

Image credit: Cell Cycle Control Group, MRC Laboratory of Medical Sciences

Read the full publication: https://link.springer.com/article/10.1186/s13073-026-01711-0