Uncovering the role of tumour microenvironments in glioblastomas 

Fast facts

• Official title: Multi-Omic Analysis of Environment-Mediated Glioblastoma Dormancy and Recurrence 
• Lead researcher: Dr Spencer Watson
• Where: University of Lausanne
• When: September 2023 – August 2027
• Cost: £600,000 over 4 years
• Research type: Glioblastoma (High grade), Tumour biology, Academic, Junior Fellowship
• Award type: Future Leaders Junior Fellowship

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The collection of cells, tissues and signalling molecules surrounding a brain tumour is known as a tumour microenvironment. 

The cells and structures within these microenvironments all have an effect on where, when and how tumours grow. They consist of different cells including immune cells, rapidly dividing tumour (cancer) cells, as well as blood vessels and normal brain cells. To complicate this further, these cells are highly dynamic and can move from one microenvironment to another. 

Cells, in all parts of the human body, communicate with one another by releasing signals and producing different proteins that can affect cell division and activity. Research has revealed that cells in the tumour microenvironment can release signals that communicate with tumour cells, contributing to their growth and survival. 

What is it?

In response to aggressive glioblastoma treatment, you often see the formation of scar-like tissue within the brain i.e. dense fibrous tissue. Dr Watson’s previous work revealed that glioblastoma cells that survive initial treatment can ‘hide’ inside these scar-like regions, and that helps to protect them from the body’s immune system and the effects of further treatment. He also showed that when glioblastoma cells are hiding in these scars, they are dormant, meaning they are not actively growing and dividing. It is only when the cells escape from these scar-like regions that they continue to spread and divide, which leads to tumour recurrence – but how they do this is completely unknown. 

In this next phase of his research, Dr Watson will use new imaging techniques to visualise and explore in immense detail the structure and composition of recurrent glioblastoma tumours and their microenvironments. He aims to understand how tumour cells in different regions respond to their microenvironment, and to pinpoint how cells moving between microenvironments can cause cell division and spread. With this knowledge, the team hope to be able to develop new treatments that specifically target dormant and recurrent tumour cells.

Why it’s important

Current treatments for glioblastoma include surgical removal of the tumour mass, radiotherapy and chemotherapy. However, eventual tumour recurrence is almost certain. Whilst frontline therapies are needed, most patients are diagnosed once tumour progression is quite advanced, and require surgery to be carried out as soon as possible. Therefore, there is an urgent need for second-line treatments that can target glioblastoma recurrence.  

Tumour microenvironments are extremely complex, and little is understood about how cells interact with one another. Dr Watson’s work aims to fill some of these knowledge gaps to enable us to better understand glioblastoma recurrence, and develop interventions that could prevent or reduce recurrent glioblastoma, ultimately offering a better prognosis for patients. 

The mechanisms by which the extracellular environment influences glioma cell proliferation represents a new class of potentially exploitable therapies. New therapies can be tailored to unique features of glioblastoma recurrence to specifically improve long-term tumour management and extend survival.

– Dr Spencer Watson