Dr. Féaron Cassidy: Are MAITs the Missing Link Between Obesity and Cancer? A Focus on Microbiota for World Digestive Health Day

What are MAITs and why do they matter?

MAIT cells, or “MAITs,” are a type of immune system cell. I’m researching MAITs because they are highly effective at killing cancer cells. I’m particularly interested in whether they play an important role in obesity-associated cancer. The number of cancers linked to obesity is increasing worldwide. Studies in Professor Andrew Hogan’s lab (where I’m hosted for the Irish leg of this research project) have shown that people with obesity tend to have fewer MAITs, and those MAITs don’t function as expected. Therefore, I want to investigate what controls MAITs and why they are negatively impacted in the context of obesity.

MAITs are part of the T cell family—but what is a T cell again?

Many people have heard terms like white blood cell, T cell, or B cell—these are different types of immune cells. MAITs are a type of T cell. When T cells sense danger, such as an infection, they become “activated” and enter fighting mode. They begin producing and releasing proteins that kill the intruder and attract other immune cells to the area to help neutralize the threat. While T cells can quickly recognize and respond to infections they’ve encountered before, they take longer to respond to new threats. For example, it can take as little as one hour to respond to a known threat, but up to 24 hours to mount a response to a new invader. This is one reason vaccines are so effective.

So, what makes MAITs special?

MAITs are a very unusual type of T cell. Not only are they rapid responders, but they also target something entirely different from most T cells. While other T cells look for previously encountered intruders, MAITs hunt for specific “metabolites.”

What is a metabolite?

A metabolite is a small molecule produced during digestion when enzymes break down food and use the components to build what our cells need. MAITs only recognize metabolites made by bacteria, so these specific metabolites act as signals that certain types of bacteria are present. These metabolites can be produced by both beneficial and harmful bacteria, and MAITs respond differently depending on the type. Our guts contain many types of beneficial bacteria, collectively known as our “microbiota.”

Do bacteria make certain metabolites that human cells don’t?

Yes! In fact, this is an important source of some nutrients. Our gut microbiota can produce B vitamins from other nutrients in our diet—something our bodies can’t do on their own. We get a significant portion of our vitamin B from our gut microbiota. MAITs recognize a metabolite produced during the synthesis of vitamin B. This ability to detect bacteria-specific metabolites allows MAITs to help maintain a balanced gut microbiota and prevent bacteria from spreading to other parts of the body.

How does all this link to obesity-associated cancer?

We’re still learning about these interactions, but the idea that our microbiota affect our MAITs aligns with existing knowledge. For example, studies have shown that people with obesity tend to have altered microbiota. This may explain why we observe fewer MAITs in the blood of people with obesity.

While we’ve primarily studied MAIT cell cancer-killing activity in laboratory settings, other researchers have found that MAITs can locate and migrate to tumors in human patients. The tumors shown in the images are from liver cancer (hepatocellular carcinoma, HCC), colorectal cancer (CRC), esophageal cancer (ESCA), and stomach cancer (STAD). CD3, TCRVα7.2, and CD161 are proteins found on the surface of immune cells. MAITs express all three, which is why they appear yellow in the images—due to the overlap of green and red markers.

What’s the take-home message?

The story of MAITs highlights how the health of our gut microbiota can impact our overall well-being. Our gut bacteria not only produce vitamin B to keep us healthy but also influence the survival and behavior of MAIT cells, which help fight cancer and infections. There are still many pieces of the puzzle to uncover before we fully understand the links between MAITs, gut microbiota, obesity, and cancer. But on this World Digestive Health Day, it’s safe to say: don’t underestimate your gut microbiota—or your MAITs!