A mixing pot of ideas: world-class immunology

​Professor Caetano Reis e Sousa was awarded the 2017 Louis-Jeantet Prize for Medicine for his outstanding contributions towards our understanding of how the immune system senses pathogen invasion and tissue damage. His latest in a long list of accolades, the Jeantet is Europe’s most prestigious prize for bioscience research.

Here, Caetano shares his thoughts on the move into the Crick, where he is a group leader, and the work currently going on in his lab.

“When the building was being designed and we were told about the collaboration spaces, and how they’d bring people out to talk to one another, some of that came across as a little bit contrived. However, it really is happening – you do see a lot more of other people, you bump into them and talk about all sorts of things, including science. Most importantly, people in different labs are talking to one another more.

The fact we have so many great people doing so many things in the building is facilitating research – somehow information just gets transmitted. Someone in my lab doing Drosophila work who wants to do some clever mutants involving conditional knockouts found that Jean-Paul Vincent is one of the world’s pioneers, so his lab has been helping us set it up. Another person is interested in protein precipitation of RNA; she discovered that Jernej Ule is a world expert, so she’s gone to talk to someone in his lab.

My lab’s work is going very well, particularly considering that we’ve only been here for six months. My research is centred around dendritic cells, the body’s professional antigen-presenting cells – we study their ontogeny and function. We’re currently excited about cancer immunology as it’s likely that some patients who don’t respond to immunotherapy treatments have insufficient numbers of primed T cells, which is a big problem. The idea is that naive T cells aren’t encountering tumour antigens, and so can’t be activated. That’s led to a resurgence of interest in exploring the role of dendritic cells in kick-starting the anti-tumour immune response.

One way that tumours evade the immune system is by producing prostaglandin E2 (PGE2), quite different from other routes that target immune checkpoints. We’ve found that PGE2 can decrease dendritic cell infiltration of tumours, which might help explain how the T cell response is impaired: if there are no dendritic cells to process and present tumour antigens, the T cells are blind to the tumour.

We already know that tumours infiltrated by dendritic cells have a better prognosis – data from mouse and man show that dendritic cell presence elicits a good immune response, and correlates with survival across different cancers. Now we’re trying to work out how to increase dendritic cell numbers in tumours; we think there’s an exciting opportunity for therapeutic intervention.

Previously at the LRI, there was understandably a strong emphasis on using cancer as a model, so there are a lot of people at the Crick who are interested in cancer. But we’re also finding people who’ve come from NIMR, who weren’t necessarily looking at cancer before, but are now identifying synergies with their research, and vice versa. There are so many interesting parallels between different diseases, for example cancer and infections, and we now have more opportunity to explore these options. It’s not just hype that being more integrated brings benefits – it really does. From Cancer Research UK’s perspective, the Crick is a very worthwhile investment: they’re getting the expertise of the whole institute.”