Sitting down to enjoy an indulgent Christmas feast? A recent study in mice by Harvard Medicine scientists found that a diet high in saturated fat can stunt immune cells, allowing cancer cells to run rampant. The fatty diet also triggers tumor cells to tweak their metabolisms, allowing them to be fueled by fat instead of sugar. This further supports their uncontrolled growth in the absence of immune push-back.
In the study, led by cell biologist Marcia Haigis and published in the journal Cell, the research team provided new insights on the impact of diet on cancer immunity. Specifically, they found a sharp decline in the presence of cytotoxic CD8+ T lymphocytes within tumors. These white blood cells play a key role in antitumor immunity via their capacity to recognize and kill malignant cells.
However, a diet high in fat cripples the ability of these immune cells to fight back against tumors. The authors managed to unravel the mechanism behind this phenomenon: tumor cells rewire their metabolisms to take full advantage of the abundance of fat (an energy-rich fuel source), which allows them to flourish, leaving “starving” T cells in their tracks.
"Putting the same tumor in obese and nonobese settings reveals that cancer cells rewire their metabolism in response to a high-fat diet," explained Haigis
"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."
Interestingly, while high-fat diets caused CD8+ cell numbers to dwindle inside tumors, this observation was not noted in other parts of the body. Inside the tumors, the team found that T cells were sluggish with extremely impaired functionality. However, once extracted and relocated to cell culture dishes, they bounced back, with immune activity normals returning to baseline. Clearly, an essential fuel source was not available to these immune cells within the context of the tumor microenvironment.
The good news is that there is a way to stop tumor cells from rewiring their metabolisms using pharmaceutical interventions.
"Cancer immunotherapies are making an enormous impact on patients' lives, but they do not benefit everyone," said a senior author of the study, Arlene Sharpe.
We now know there is a metabolic tug-of-war between T cells and tumor cells that changes with obesity, says Sharpe.
"Our study provides a roadmap to explore this interplay, which can help us to start thinking about cancer immunotherapies and combination therapies in new ways."
"Our study provides a high-resolution metabolic atlas to mine for insights into obesity, tumor immunity, and the crosstalk and competition between immune and tumor cells. There are likely many other cell types involved and many more pathways to be explored," added Haigis.