Diet and cancer: New study shows how high-fat diet promotes tumour growth in mice

A microscopic image of a normal mouse small intestine. Cells stained red express normal amounts of cell-surface tags (MHC-II) needed by immune cells to find threats like infections or cancer. High-fat diets reduce the levels of MHC-II tags in intestinal cells. Photo: Beyaz lab / Cold Spring Harbor Laboratory

What we eat is hardly talked about as contributing to the formation and growth of tumors. A new study has found that a high-fat diet increases the incidence of colorectal cancer, which starts in the colon or the rectum and grows to other parts of the body.

Fat disrupts the relationship between intestinal cells and the immune cells that watch them for emerging tumors, according to researchers from Harvard Medical School and the Massachusetts Institute of Technology. The study was published in journal Stem Cell Stem September 15, 2021.

What we eat is an important part of understanding environmental risk factors that affect the incidence of cancers, Cold Spring Harbor Laboratory Fellow Semir Beyaz had stated in his earlier studies. He is the lead author of the current study as well.

At the center of this study were the MHC-II tags, which distinguish between normal and abnormal cells.  MHC-II encodes a protein that presents antigens, or foreign substances, to the immune system. When a cell is infected, immune cells detect the foreign particle by watching over these MHC molecules.

MHC cells activate the immune system to destroy bad cells — in case they are wearing out or about to become cancerous. But a high-fat diet suppressed MHC-II levels in intestinal cells in mice, the study found.

Hence, cells with reduced levels of these tags could not be identified as abnormal and hence, could grow into tumors.

Beyaz said the crosstalk between stem cells, microbes and immune cells is critical for eliminating tumor-initiating cells. But this cross-talk can fail in response to a high-fat diet.

So what should be done? “If we alter the level of these immune recognition molecules in a positive way, then the tumor will more likely be recognized by the immune cell. We hope this can be coupled with the existing strategies, such as immunotherapy, to eradicate tumors,” Beyaz said.

The level of immune recognition molecules can be done by increasing the production of this MHC-II tag — either by diet, drugs or changing the microbes in the body — can help the immune system recognise and eliminate cancer cells. 

Beyaz’s 2018 study at Harvard looked at the relationship between high-fat diets and the production of stem cells in the intestine. He found that overproduction of stem cells resulted in a higher rate of tumor incidence of colorectal cancer in mice. 

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