Does Obesity Affect Immunity?

New research from Harvard Medical School warns obesity could impair the function of immune cells and potentially accelerate tumour growth. Citing competition for fuel as a key driver, scientists warn a high-fat diet could allow cancer cells to outperform immune cells and spread within the body. The study builds on existing research suggesting links between obesity and more than a dozen different types of cancer, with scientists previously exploring drivers such as chronic inflammation and metabolic changes.

Working from Harvard Medical School, the team conducted studies on mice to uncover new insight into the relationship between obesity and cancer. The results could spark exciting change for cancer immunotherapy, with the team noting obesity allows malignant cells to outperform a critical type of tumour-killing immune cell known as CD8+ T. Used in many different types of immunotherapies, CD8+ T kickstart the immune system and play a critical role in defencing cells against intracellular pathogens.

"CD8+ T cells are the central focus of many promising precision cancer therapies, including vaccines and cell therapies such as CAR-T," says co-senior author Arlene Sharpe.

High-fat diets compromise CD8+ T performance

When exposed to high-fat diets, cancer cells adjust their metabolisms and begin to devour energy-rich fat molecules. This deprives CD8+ T cells of fuel, hindering activity and promoting cancer growth.

"Putting the same tumour in obese and nonobese settings reveals that cancer cells rewire their metabolism in response to a high fat diet,” comments Marcia Haigis, co-senior author of the study and a professor of cell biology in the Blavatnik Institute at Harvard Medical School. "This finding suggests that a therapy that would potentially work in one setting might not be as effective in another, which needs to be better understood given the obesity epidemic in our society."

A “metabolic tug-of-war”

The findings were published in the scientific journal Cell, with the team noting that blocking the metabolic reprogramming abilities of cancer cells significantly reduced rates of tumour growth. Co-senior author Arlene Sharpe compares the process to a “metabolic tug-of-war between T cells and tumour cells” and says the study empowers scientists with a “roadmap” to explore the interplay between the two processes. Ultimately, the hope is to use the research to develop new cancer immunotherapies, as well as promote the importance of a healthy lifestyle and diet.

"We're interested in identifying pathways that we could use as potential targets to prevent cancer growth and to increase immune antitumor function," adds Haigis. "Our study provides a high-resolution metabolic atlas to mine for insights into obesity, tumour immunity and the crosstalk and competition between immune and tumour cells. There are likely many other cell types involved and many more pathways to be explored."

To find out more about the latest cell-driven research, and to gain insight from experts such as Marie-Charlotte Manus, Dr Louise Bonnemay and Matthieu Opitz, don’t miss ‘Micropatterning: The art of micro-controlling cells.'