EACR 2016
Connections in cancer-host immune signalling
Dr Alan Serrels - University of Edinburgh, Edinburgh, UK
I presented new insights into how cancer cells communicate with the tumour immune environment in order to orchestrate an immunosuppressive environment that suppresses anti-tumour activity.
What did you find?
We presented a novel role for a protein called focal adhesion kinase which is frequently upregulated in human tumours. What we identified is that specifically in cancer cells it can translocate to the nucleus where it takes on a new function of controlling the transcription of chemokines and cytokines into soluble factors that get secreted from the tumour cells that communicate out through paracrine signalling networks to immune cells and in particular regulatory T-cells which then suppress the activated CD8 T-cell response and permit tumour growth.
Was there a particular cancer you focussed on?
The work was primarily done in squamous cell carcinoma of the skin and we’re currently expanding those findings out to other tumour types to establish the relevance more broadly in cancer.
Would you expect to observe similar things in other cancer types?
Yes, so preliminary studies would tell us that we expect to see similar functions, the modulation of the tumour immune environment and response to targeting FAK.
What methods did you use to get to your findings?
We used a combination of transplantable tumour models, genetic deletion of focal adhesion kinase in the tumour cells of interest, and flow cytometry, transcriptional profiling and proteomics.
What do you think the clinical implications will be?
As a consequence of the research that we published late last year, opening in the third quarter of this year, expected to open in the third quarter of this year, is a multi-centre, so five centres across the UK, a clinical trial to look at the potential clinical benefits of combining FAK inhibition with checkpoint blockade in non-small cell lung cancer, pancreatic cancer and mesothelioma.
When will you see the results of this trial?
Probably we would know towards the end whether we had clinical benefit. What we will get as the trial progresses is biopsy samples both pre- and post-treatment in order to be able to look to see if the findings that we established in our pre-clinical models translate through to the human setting. So if we see modulation of the tumour immune environment in response to FAK inhibition and then I suspect that at the end, maybe two years from now, we would start to understand whether there are benefits for patients.
Is there any other work ongoing?
I have a small lab so at the moment we’re quite focussed on understanding this role; we think that it’s broader than what we’ve published so far. So we’re interested in trying to understand that more so that we could start to expand out to look at other aberrantly regulated pathways in cancer cells that may control chemokines and cytokines and whether they also could be advantageous to targets.
