It’s NF2 science, but summarised! Visit the previous blog post in this series:
Science Summarised: Potential New Drugs for Hearing Loss
This blog was written by NF2 BioSolutions PhD student Grace Gregory.
[Image Description] Grace Gregory in the laboratory at the University of Manchester.
—
People with NF2-related schwannomatosis (known as NF2 and previously called Neurofibromatosis Type 2) can develop multiple tumour types, the most common being vestibular schwannoma that grow in the auditory canal as described in our previous ‘Science Summarised: Potential New Drugs for Hearing Loss’ blog.
Second to vestibular schwannoma come meningioma, which are tumours that grow from the strong membrane that usually functions to cover and protect brain and spinal cord. This means that people with NF2 have the possibility to develop meningioma within the skull and along the spine which can cause difficulty with movement, seizures and vision depending on their location.
That’s why understanding the genetics behind NF2-associated meningioma, how they are treated, and what they are composed of is very important… and this is what we covered in our recent published review article that was part-funded by NF2 BioSolutions UK and Europe through the authors Grace Gregory and Adam Paul Jones (NF2 BioSolutions PhD students) and summarised in this blog.
[Image Description] Journal title for the full open access published article summarised in this blog, titled “The clinical, genetic, and immune landscape of meningioma in patients with NF2-schwannomatosis” by Gregory et al 2023.
Meningioma Genetics:
Genes are like words, i.e made up of individual components (like letters) that when read together make sense. For example, the word ‘NOW’ is made of N, O, and W. If we change a letter, for example W to T then it changes the meaning of the word to ‘NOT’. This can happen with genes too. If one part of a gene is changed then it may alter its function or make it not work altogether…
The NF2 gene usually functions to inhibit tumour growth but if a change occurs in the NF2 gene that prevents this important function then tumours may be allowed to grow. Approximately 50% of people with NF2-schwannomatosis have inherited a faulty version of the NF2 gene from a parent.
The NF2 gene in the other half of people with NF2-schwannomatosis may have become faulty when they were developing in the womb and so not all their body’s cells will be affected (this is known as mosaic NF2).
But how do the changes in the NF2 gene affect meningioma? Well, the location of the change in the NF2 gene can influence the likelihood that a meningioma will develop. For example, a faulty change at the start of the gene can increase the risk of developing a meningioma, whereas people with changes nearer the end of the NF2 gene have a lower risk.
Meningioma Composition:
It’s true that meningioma develop from the cells in the membrane that protect the brain and spinal cord, however tumours have many more components to them. These tumour cells are surrounded by a meshwork of fibres that organise the tumour structure and aid immune cells in their invasion into the tumour. The immune cells have different functions from the assassins of the immune system (known as T-cells) that seek out abnormal cells to kill them, to the clean up crew (known as macrophages) that engulf dead cells and debris and promote a healing response.
[Image Description] Diagram of the assassin role of T-cells killing abnormal cells and the clean-up role of macrophages that then release inflammatory molecules to recruit more immune cells.
However tumours can alter immune cell behaviour, supressing the killer functions of T-cells and hijacking the healing response of macrophages to instead promote tumour growth.
[Image Description] Diagram of the components of meningioma, with the blood vessels and fibrous meshwork that allow immune cells (such as T-cells and macrophages) to infiltrate into the tumour.
Meningioma Management:
For people with NF2-schwannomatosis, a strategic observation approach might first be employed to identify if the meningioma is growing.
[Image Description] MRI scans of meningioma growth patterns, either dormant quiescent/no growth, saltatory leaps, consistent linear growth, or rapid exponential growth.
If treatment is required, the first-line treatment is surgery for symptomatic and fast-growing tumours. Radiotherapy and radiosurgery may be required for meningioma in difficult locations and unfortunately if they grow back after surgery.
New therapeutics that target signals and components of the tumour that promote tumour growth are in clinical trails for meningioma although none yet that look at the immune system. Therefore, future studies should look towards the immune cells that invade into meningioma as potential therapeutic targets.
—
This blog has been created as a way to share stories, ideas, positivity and even sprinkle in some science. Everyone is welcome here and warmly encouraged to join us in contributing to our community through this blog. If you would like to add anything (anything at all!) then please contact myself, Grace Gregory, at grace@nf2biosolutions.org and we can pop it up on our blog. Watch this space and please join in helping us all connect and share with one another!