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Using the immune system to fight tumours – the foundation of immunotherapy – has transformed the way we fight cancer. While this approach has brought hope to thousands of patients, unfortunately, it is not a one-size-fits-all solution. Understanding why certain patients do not respond to immunotherapy and how to overcome this roadblock are two big questions puzzling health researchers – and answering them requires a multidisciplinary approach.

Sebastien Talbot (Biomedical and Molecular Science) has spent the past eight years working on the intersections between immunology, neuroscience, and cancer research. A member of the Sinclair Cancer Research Institute, he shared with the Gazette how his research journey led him to explore how the nervous system might have an important role to play in treating tumours. The interview has been edited for clarity and length.
 

Why should we study the nervous system and the immune system together?

It has been long appreciated that the nervous system, particularly sensory neurons, are involved in detecting danger from the environment – for example, when you touch something very cold or very hot. The pain we feel thanks to these neurons warns, via withdrawal reflexes, our muscles to get out of a dangerous situation as quickly as possible to avoid extra damage.

The immune system is also involved in protecting us, but in a different way. It detects bacteria and viruses and produces responses against them to prevent infection. In a nutshell, both systems co-evolved to be highly complementary and ultimately protect our bodies from external danger. Early studies in neuroimmunology looked at what happens in our bodies when fighting bacterial infections.
 

What drove your attention to neuroimmunology in cancer research?

The discovery that there are blood vessels growing within tumours transformed cancer research. These blood vessels bring nutrients to the cancer cells, helping them grow and eventually, spread through the body. In mammals, blood vessels usually grow in close proximity with nerves. In 2013, during my post-doc, I read an important paper showing that prostate tumours had sympathetic nerves within them. That sparked my curiosity, and I decided to study whether tumours contained pain-transmitting neurons – .

What does that mean for how we understand and treat cancer?

We were able to show that sensory neurons grown in or near tumours interact with immune cells and that this interaction is very negative for cancer patients, because immune response triggered by these tumour-associated nerves can . They reduce the chance for patients to respond to therapy. So, we are looking for ways to avoid that.

Specifically, our research is looking at the calcitonin gene-related peptide (CGRP), which is a neurotransmitter produced by sensory neurons that acts as a chemical messenger between the nervous system and the immune system. We want to test if blocking CGRP would be helpful for cancer patients undergoing immunotherapy.
 

How are you planning to do that?

There are drugs currently in use for migraines that target CGRP-receptors, and we want to see if patients taking these drugs would respond better to their cancer treatments – preliminary results in different types of cancer suggest so. Our plan is to look at different drugs used in neurological diseases, such as Alzheimer, depression, Parkinson’s, and see if they can be .

Our team is currently studying melanomas. As a first step, we are assessing the presence of nerves within these tumours to see which patients could benefit from a study like the one we are proposing. Then, I expect we will be able to move on to clinical trials.
 

Cancer neuroscience is a rapidly growing field – what makes you most excited about it?

The field has been really exploding, and each week we see new, exciting research results being published. Our team recently published , and how we could potentially reverse that by, for example, targeting nerve cells within the tumour.

Researchers around the world have been identifying these neuro-immune associations across different types of cancer, and I believe we are very close to see how beneficial it would be to target neurons in cancer treatment – just like we target immune cells and blood vessels.