What path led you to the Faculty of Medicine?

Originally from Bellinzona, I studied medicine in Bern before doing an MD-PhD at the Ludwig Institute for Cancer Research in Lausanne, in the field of tumour immunology. After a postdoc in Bern and several years in Lausanne with an Ambizione grant followed by an SNSF PRIMA position, I joined Geneva in 2020 as an assistant professor. I’ve just been promoted to associate professor and I’m also a member of several faculty and interfaculty centres – CRTOH, GCIR, iGE3, and also the Ludwig Institute in Lausanne – which allow for real synergies and an openness towards translational and clinical medicine. It’s genuine added value for research.

As a basic science researcher, you’ve never practised clinical medicine. Why did you choose to study medicine rather than biology?

I needed to understand human physiology and pathophysiology as a whole, before deciphering their cellular and molecular mechanisms. That training still shapes my approach towards translational research today. With my team, we receive samples every week from HUG patients, which we study in detail to develop solutions that can be applied in the clinic. This back-and-forth between the laboratory and the clinic is, for me, essential.

What fascinates you about cancer immunotherapy?

Unlike chemotherapies, which destroy cells in a non-specific way, immunotherapy harnesses the immune system’s natural ability to protect the body against harmful threats. In the context of cancer, those threats are malignant, transformed cells. Cancer immunotherapy works by strengthening and directing the immune response specifically against tumours. It’s about giving the body back its own strength to eliminate cancer cells. This approach is both elegant and promising, with still so many avenues of research to explore! For instance, in the project funded by the Leenaards Foundation that I’m co-leading with Li Tang from EPFL and Olivier Michielin (UNIGE & HUG), we’re shifting from conventional biochemical interactions towards physical principles, to decipher the mechanical interactions between immune cells and tumour cells. Recent findings indicate that the stiffer the tumour cells, the more easily the immune system can eliminate them. So, our goal is to decipher the underlying mechanisms and find a way to stiffen tumours in vivo, for example via nanoparticles delivering messenger RNAs to selectively modify gene expression. Our immune defences are still far from having revealed all their secrets!

What role does the Geneva ecosystem play in your research?

An essential one. CRTOH, in particular, has created a genuine community bringing together different areas of expertise while strengthening the link with the hospital. Through grants like the GTO Awards (Geneva Translational Oncology), researchers are paired with clinicians to carry out joint projects. The centre also has state-of-the-art instruments for analysing patient tissue samples at the single-cell level. By combining the data generated by the different teams in the network, we reach a critical mass that enables powerful analyses using artificial intelligence algorithms. The aim is to integrate clinical, histological and genomic data in order to better predict and tailor treatment response for each individual patient.

More recently, you’ve been exploring the links between the brain and the immune system through virtual reality. How did you come to that?

The idea, which came out of discussions with neuroscientists at UNIL, isn’t actually that recent. But it took us a while to demonstrate its validity! The brain and the immune system both respond to danger signals, but for a long time they were studied separately. Our hypothesis was that the mere visual perception of signs of illness could preventively activate the immune system, even before contact or real infection. In a nutshell, if I see someone with visible signs of disease, my brain is already alerting my immune system to get ready to react.

To test this idea, we used virtual reality, which allows us to deliver purely visual stimuli, with no confounding factors. We exposed healthy participants to avatars, some of which showed signs of infection taken from photographs of sick patients, others showed signs of stress, and others had a healthy appearance. The results, published as a cover article in Nature Neuroscience, confirm that there is indeed a specific activation of dedicated brain areas and of the sentinel cells of innate immunity in response to the ‘sick’ avatars. And we also showed that this immune activation was responding to signals sent by the brain, which differed depending on the avatars.

What are the next steps?

The next step is to determine how specific this system is and to assess its potential therapeutic applications. To support this, we’ve photographed historical moulages of infectious diseases from the past 150 years at the Moulage museum in Zurich, to generate new avatars. The aim is to analyse whether the brain can discriminate between different types of pathogens – viral, bacterial, fungal – and accordingly alert different types of immune responses. We also aim at identifying whether the immune response is a reactivation of immunological memory or a newly generated response. This will be tested by comparing reactions to avatars displaying familiar diseases, like herpes, and historical diseases like the plague, to which we’ve never been exposed.

A CONFIRM Priority grant from the HUG Private Foundation is precisely aimed at exploring therapeutic applications of this discovery, in the field of allergies…

In collaboration with Peter Jandus, an allergologist at HUG, Oliver Kannapé from the VR Center of HUG and Andrea Serino, neuroscientist at CHUV/UNIL, we’re testing if a VR-approach could serve as a therapeutic alternative for desensitization to Hymenoptera venom, such as bees and wasp stings. In this study, patients are immersed in a virtual environment populated by bees (or control animals) and then ‘stung’ virtually with a mild stimulus on their skin. Neuro-immune biomarkers are monitored and compared both to responses elicited to control stimuli and those observed with conventional desensitisation protocols. If the results are conclusive, we’ll repeat the exposures as in conventional desensitisation, to train the immune system towards tolerance.

In my view, the neuro-immunological dimension of somatic diseases hasn’t been studied nearly enough. For example, some individuals with food allergies develop hives simply by seeing the food – without any contact with the allergen. What’s happening between their brain and their immune cells? The potential applications of this line of research are vast: autoimmune and inflammatory diseases, cancer, and even vaccination – you could imagine a first conventional vaccine injection followed by booster doses in virtual reality, without complex logistics or cold chain requirements. With a major advantage: no need to travel, a VR headset at home would suffice, and you’d also limit potential pharmacological side effects.

Has it been easy to get these rather unconventional lines of research accepted?

Not really! It was perhaps a bit too original. But we persevered and developed extremely rigorous research protocols. From a career standpoint, committing on such high-risk projects without the security of a stable academic position is challenging, and many scientists would not necessarily recommend it. However, I’ve always believed you must dare to follow your scientific convictions – and I’m delighted to be reaping the rewards of that perseverance today. I now want to explore more deeply into the connections between neuroimmunology and cancer: understanding how the nervous system and neurotransmitters influence tumour growth and immune infiltration in patients and harnessing virtual reality or other neural stimulations to improve their treatments. This is an entirely new field in humans.