It’s NF2 science, but summarised! The previous blog posts in this series:
Science Summarised: Potential New Drugs for Hearing Loss
Science Summarised: All Things Meningioma
This blog was written by NF2 BioSolutions PhD student Grace Gregory.
[Image Description] Grace Gregory in the laboratory at the University of Manchester.
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Exciting news! We have a new NF2 BioSolutions UK funded research paper out! Find the full open access paper here or read the blog below for a bite-sized version open to a non-scientific audience.
Also if you are interested in watching a video summary of the paper then just follow the full open access paper link, scroll down the page to find the video abstract!
[Image Description] Paper header for paper titled “The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma” by Gregory et al 2023, published in Brain Communications.
PAPER BACKGROUND:
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. Vestibular schwannoma were previously also known as acoustic neuroma.
[Image Description] Vestibular schwannoma tumours develop from the Schwann cells that wrap around the auditory nerve.
As an NF2 research team funded by NF2 BioSolutions UK and Europe we want to understand how vestibular schwannoma grow so that appropriate clinical trials and drug choices can be made. NF2 is a rare condition found in about 1 in 33,000 people which means that clinical samples such as tumour tissue can be scarce for researchers to collect. However, vestibular schwannoma are much more commonly found in people without NF2 (with no hereditary connection) which are known as sporadic vestibular schwannoma.
[Image Description] Sporadic vestibular schwannoma grow on one side only with no other tumours, whereas NF2 vestibular schwannomas grow on both auditory nerves and can be joined by other tumours such as meningioma, ependymoma and non-vestibular schwannoma.
In this recent published research paper we investigated the similarities and differences between sporadic and NF2 vestibular schwannoma as we hypothesise that similarities in these tumours from both the NF2 cohort and sporadic cohort could allow them to be co-recruited to the same clinical trials. Also, drug treatments and immunotherapies that are effective in one set of people may be applicable to other. And finally, research findings in the samples from one group (i.e the more common sporadic vestibular schwannoma samples) may be applicable to the other group which could widen the pool of research resources available.
[Image Description] Benefits of similarities between NF2 and sporadic vestibular schwannoma include same clinical trials, treatments and the research in one being applicable to the other.
As we are part of an inflammation-focussed group, we are not only interested in the Schwann cells (the tumour cells that grow and multiply to form the main bulk of the tumour) but also the body’s immune cells that invade into the tumour itself. Usually, immune cells function to protect the body by clearing infections and abnormal cells (like tumour cells). They work together as 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.
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 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.
PAPER AIMS
To investigate NF2 and sporadic vestibular schwannoma, we compared:
- their “gene expression” (i.e what is active in the tumour, for example genes associated with growth and immune cells),
- any differences in signalling pathways (i.e what communication is going on within the tumours),
- the cell abundance (number and types of tumour cells and immune cells present),
- and localisation/niches of where the immune cells are likely to be found within the tumours (i.e are they close to each other, to the blood vessels, to a specific type e.g macrophages and T-cells together?)
PAPER RESULTS:
What did we find?
We found no robust differences between NF2 and sporadic vestibular schwannoma, instead finding that NF2 and sporadic vestibular schwannoma were highly similar in their gene expression, signalling pathways, cell abundance and immune cell niches.
Our paper reinforces the hypotheses that people with NF2 or sporadic vestibular schwannoma may benefit from the same drug treatments, co-recruitment to the same clinical trials and that research using samples from one group may be applicable to the other.
[Image Description] Final results from the paper show that NF2 and sporadic vestibular schwannoma tumours are highly similar, both being primarily composed of Schwann cells (about half of the tumour) and macrophages (about a third of the tumour).
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This blog has been created as a way to share real 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!