The importance of your MAITs – Dr Féaron Cassidy tells us about her placement in Stockholm
Posted: 3 October, 2024
A few short weeks ago, I arrived in Stockholm at the Karolinska Institutet (KI). KI ranks number 16 in the world, and number 1 in Europe on the Times Higher Education list of universities leading in medicine, dentistry and other health subjects in 2024 (1). It is also the institution where the Nobel Prize in Physiology or Medicine is appointed, so it is a really exciting place to be kicking off my first fellowship!
In my research, I aim to understand the link between cancer and obesity. We know that there is a higher risk of cancer in the population of people who live with obesity – but it is less clear exactly why, and also how this could be prevented or reduced. Current recommendations for reducing obesity-associated cancer revolve around losing weight through diet and exercise. Not only is this an overall unsuccessful method of weight loss for the majority of people (2), but there is also no convincing data that weight loss reduces the risk of cancer (3,4). My goal is to find out how obesity and cancer are linked and explore ways to reduce cancer incidence and mortality in the future.
In order to do this, I am focusing on the immune system, as immune cells play an important role in finding and killing cancer cells, and because we know that there are often changes in the immune system when we look at the immune cells from people with obesity. I am working to understand how adipose (fat) cells and immune cells interact, and how their interactions may affect the ability of immune cells to kill cancer cells.
MAIT CELLS AND THE SCIENCE OF OBESITY
The immune cells that I am particularly interested in are called MAIT cells. MAIT cells are an unusual type of T cell, and I have been studying them for a few years now. At Maynooth University (MU), where I worked from 2020-2023, and where I will spend the second half of my fellowship, we collaborate with Prof. Donal O’Shea who is the HSE National Lead for Obesity. People who attend clinics specifically for obesity-related support may be asked to donate blood or adipose tissue for our research during routine blood testing and/or during bariatric surgery. We are extremely grateful to the clinicians and the individuals attending the clinics, because these donated samples have allowed us to uncover a stark reduction in MAIT cells related to obesity (5). I found that MAIT cells are very effective at killing cancer cells and I now want to know how and why they are diminished in people with obesity.
One of my findings so far in relation to MAIT cells has been how they get the energy they need to kill cancer cells. I discovered that MAIT cells do not need to take in sugar to fuel their ability to kill cancer cells; instead, they make a starch called glycogen which they can then use when they need it (6). This ability of MAIT cells to bring their own “packed-lunch” shows just how useful MAIT cells could be in fighting cancer.
ACCESS TO CUTTING EDGE TECHNOLOGY
The reason I am looking specifically at the interactions between these MAIT cell and the adipose is that adipose tissue is the major tissue effected in obesity, and because I have already found clues that adipocytes (fat cells) are signalling to MAIT cells. This is where the exciting technology available at KI comes into play. One of the experiments I will conduct at KI involves using their MACSima machine to look at adipose tissue from individuals with obesity compared to those without obesity. The MACSima machine allows us to see the proteins expressed by each cell in a tissue slice.
A very thin slice of the adipose tissue donated by a patient is placed on a glass microscope slide and analysed by the MACSima. This is similar to how tissue would be analysed with a microscope, for example by a pathologist checking if a tissue is cancerous or not. Previously, we could look at the shapes and distribution of the cells in the tissue, and identify a handful of proteins in the tissue. However, we could never integrate the large-scale information from the tens or hundreds of proteins that might be important in diseases like cancer with our ability to see where the changes are happening spatially. The MACSima allows us to do this.
The technology and expertise at KI will be instrumental in my project, which shows how important international collaborations are in research. I am also bringing knowledge to KI, where the lab group is interested in gaining a better understanding of how other types of immune cells fuel their actions. With my previous experience in Dr. Hogan’s lab (MU), where I worked on the use of glycogen by MAIT cells, I will be able to provide insight into this area called “immunometabolism” for Prof. Björkström’s group at KI. Dr. Hogan and Prof. Björkström are my two supervisors for this project.
All in all, the opportunity afforded by the DOROTHY COFUND fellowship to work with a world-class team using cutting-edge technology will be transformative for my research.
2 https://www.mdpi.com/2072-6643/14/6/1259
3 https://www.bmj.com/content/359/bmj.j4849.long
4 https://onlinelibrary.wiley.com/doi/full/10.1002/oby.22936
5 https://pubmed.ncbi.nlm.nih.gov/31076528/
6 https://www.pnas.org/doi/abs/10.1073/pnas.2300566120