How a Fellowship helped Dr Mike Coleman uncover links between obesity, the immune system and cancer

Dr Mike Coleman’s research sits at the intersection of cancer, metabolism and the immune system. But when he first began his Marilyn Gentry Fellowship at the University of North Carolina at Chapel Hill back in 2022, the path ahead was far less defined.

“My work concerns the idea that the body’s natural immune system is actually really good at controlling cancer most of the time,” says Dr Coleman. “This means thatby the time someone gets a cancer diagnosis, it is usually indicative that their immune system has been tricked in some way by cancer.”

For over 25 years, the AICR/WCRF Marilyn Gentry Fellowship has supported emerging leaders in the field of diet, nutrition and cancer, funded by the American Institute of Cancer Research. Under the guidance of Professor Steve Hursting, a global expert in the field of nutrition and cancer, Dr Coleman was able to approach his research with real creativity. The fellowship gave him the freedom to explore and follow an emerging question that continues to define his research: how does obesity affect the immune system’s ability to fight cancer?

From early inspiration to impact

Dr Coleman’s interest in science began early. Growing up on a farm, he found himself drawn to problem-solving, and to understanding how diseases develop at a molecular level.

That curiosity led him to study biochemistry, before focusing his PhD on how mitochondria influence the spread of breast cancer. “I wanted to deep dive inside the cell and say, ‘what’s going on at this level?’” says Dr Coleman.

It was during his PhD that he first encountered the strong links between obesity and cancer risk, an observation that would later guide his fellowship research. And at this same time, he decided to expand his research from looking at a single cell towards whole body metabolism.

Investigating adoptive cell therapy

By the time Dr Coleman started the AICR/WCRF fellowship, it was clear that the immune system was going to be central to his work, which brought his attention to what we know as CAR T cell therapy.

CAR T-cell therapy is a groundbreaking form of immunotherapy, also called adoptive cell therapy, that modifies a patient’s own immune cells to recognise and destroy cancer cells. “You take some blood from the patient and then re-engineer a certain set of immune cells to specifically target cancer cells. These cells can then be re-introduced to the patient and hopefully control the cancer growth,” says Dr Coleman. “I like to think of it as putting them through a cancer-killing boot camp so that when they re-enter the body, they are ready to attack tumour cells.”

While CAR-T cell therapy works very well with blood cancers, they are far less effective against solid tumours, such as breast cancer or colon cancer. “And I wanted to explore how obesity interacts with that,” says Dr Coleman.

Testing his hypothesis on triple negative breast cancer cells, his research showed that obesity-related inflammation can impair the ability of CAR-T cells to destroy tumours, thereby dampening their anti-tumour effects.

Overall, the findings highlighted obesity as an important but often overlooked factor influencing cancer immunotherapy outcomes. With 40% of Americans having obesity, Dr Coleman believes that understanding the role of obesity, and approaches to improve metabolic health, in immunotherapy response will be critical to maximize the potential of next cancer treatments.

Can weight loss affect tumour growth?

As part of Dr Coleman’s work to better understand the impact of obesity on the immune system, he wanted to determine whether weight loss has the potential to restore immune function.

Looking retrospectively at cancer incidence in people who have had bariatric surgery, there’s about a 30-50% reduction in obesity-driven cancer rates in women who have this procedure. “We wanted to understand whether there is something unique to bariatric surgery that is driving the kind of weight loss that sees these special benefits,” says Dr Coleman.

Using mouse models, they compared different weight loss approaches – including bariatric surgery and dietary changes – and examined their effects on tumour growth.

“Long story short is that the extent of weight loss, independent of how you got there, was really a major predictor of how protective an intervention was going to be,” says Dr Coleman.

They found that all forms of sustained weight loss reduced tumour growth and helped restore anti-tumour immune activity, but calorie restriction produced the strongest protective effects. Importantly, the study showed that the amount of weight and fat lost, rather than the specific method used, was a major driver of improved immune function and reduced cancer progression.

“It really set up this idea for me that losing weight has this potentially potent effect to fire the immune system up to control tumour growth,” says Dr Coleman. “And now we understand a lot more about the ways the immune system is dampened by obesity, and why that weight loss then might be so protective.”

A rapidly changing landscape

These findings are becoming even more relevant as new weight loss medications, such as GLP-1 receptor agonists, continue to transform the treatment landscape.

“In the past, sustained weight loss at this scale was mostly limited to bariatric surgery,” he says. “In general, folks who are eligible for bariatric surgery typically don’t undertake it, but we’re now entering an era where these medications are widely used and well tolerated.”

Interventions to study weight loss are generally hard to do. The game-changing feature with GLP-1 medications is that they are relatively well-tolerated and, in general, popular amongst people who are eligible for them. This opens new possibilities for cancer care. A recent publication found that GLP-1 use was significantly associated with improved survival and reduced recurrence among breast cancer patients with obesity.

Researchers can now begin to explore how weight loss interventions might be combined with immunotherapies to improve outcomes.

“This means we’re entering an era where you can now realistically imagine a case of standard oncology treatment where we begin to ask, ‘how do we incorporate Tirzepatide or other weight loss drugs into that care?” says Dr Coleman. “And ‘how can these drugs be used to protect immune function?’, or even ‘how can it synergise with therapies that we know are going to promote immune response?’”

Advice for future scientists

For his next research question, Dr Coleman is approaching adoptive cell therapies as an area of potentially huge growth for solid tumour oncology.

“Is there a way to customise adoptive cell therapy to be responsive to body weight or body composition?” he says. “The overall goal is to overcome obesity-driven resistance by customising the therapy or integrating interventions like GLP-1 drugs to protect immune cell function.”

Dr Mike Coleman (centre) with Dr Giota Mitrou (left) and Dr Helen Croker (right) from WCRF International.

Dr Coleman says that the fellowship gave him the security to chase the questions that sparked curiosity in him and allowed him to be a little more fearless.

When thinking about advice for early career researchers, Dr Coleman encourages scientists to think outside of their own silos. He says that the days of one lab solving a problem in isolation is waning, and projects are now being executed in bigger, broader teams. “Dipping a toe in the other research pools gives you a lot back and it will naturally create a network of people you could collaborate with in the future.”

By the end of his Marilyn Gentry Fellowship, Dr Coleman had not only built an extensive body of research, publishing over 20 papers, but helped strengthen the idea that obesity directly suppresses the body’s ability to fight cancer, and that restoring metabolic health could improve responses to future cancer treatments and immunotherapies.

“This fellowship didn’t just support my research,” he says. “It helped to shape the future direction of my career.”

Currently Dr Coleman’s work, at UNC Chapel Hill, continues to further understand how weight management and metabolic approaches can be used to revitalise immune response in cancer.