Science & Technology

How High-Fat Diets Allow Cancer Cells To Go Unnoticed by the Immune System

A microscopic picture of a standard mouse small gut. Cells stained purple specific regular quantities of cell-surface tags (MHC-II) wanted by immune cells to search out threats like infections or most cancers. Excessive-fat diets cut back the ranges of MHC-II tags in intestinal cells, and so the immune system has a tougher time recognizing intestinal tumors. Credit score: Beyaz lab/CSHL, 2021

The immune system depends on cell floor tags to acknowledge most cancers cells. CSHL researchers found mice who ate high-fat diets produced much less of those tags on their intestinal cells, suppressing the skill of immune cells to determine and get rid of intestinal tumors. The high-fat food regimen additionally diminished the presence of sure micro organism in the mice’s intestine, which usually helps keep the manufacturing of those tags.

A high-fat food regimen will increase the incidence of colorectal most cancers. Chilly Spring Harbor Laboratory Fellow Semir Beyaz and collaborators from Harvard Medical Faculty and Massachusetts Institute of Know-how have found that in mice, fats disrupts the relationship between intestinal cells and the immune cells that patrol them searching for rising tumors. Reconfiguring the intestine microbiome could also be a solution to heal the relationship.

The immune system patrols tissues searching for and eliminating threats. Sure immune cells search for tags that distinguish between regular and irregular cells. One tag, referred to as MHC-II, helps goal cells for destruction. Cell-surface MHC-II prompts the immune system to destroy that cell, whether or not it’s simply worn out or about to develop into cancerous. Beyaz and his colleagues discovered that when mice ate diets excessive in fats, MHC-II ranges have been suppressed in intestinal cells. Cells with diminished ranges of those tags weren’t acknowledged as irregular and thus might develop into tumors. Charlie Chung, a Stony Brook College graduate student-in-residence in Beyaz’s lab, says, “If we alter the degree of those immune recognition molecules in a constructive method, then the tumor will extra probably be acknowledged by the immune cell. We hope this may be coupled with the current methods, akin to immunotherapy, to eradicate tumors.”

Intestinal cells of a mouse that have been fed a high-fat food regimen. The intestinal cells specific much less of the MHC-II tag than present in a intestine from mice fed a standard food regimen. Credit score: Beyaz lab/CSHL, 2021

The researchers discovered {that a} high-fat food regimen modified the mouse’s intestinal microbiome (the combination of microbes in the intestine). A number of micro organism, together with ones referred to as Helicobacter, enhance MHC-II, which can assist immune cells find irregular cells. The workforce did a “soiled roommate” experiment the place mice with out these micro organism have been housed with ones that had it. The “clear” mice grew to become contaminated with the Helicobacter micro organism and produced extra of the MHC-II tag.

The scientists’ findings counsel a brand new solution to enhance present immunotherapy remedies towards most cancers. Growing the manufacturing of this MHC-II tag, both by food regimen, medicine, or altering the microbes in the physique, might help the immune system acknowledge and get rid of most cancers cells. Beyaz says:

“This interplay between food regimen, microbes, and immune recognition has the potential to assist us clarify how way of life components can contribute to tumor initiation, development, or response to remedy.”

Cancer cells use many methods to keep away from being acknowledged as irregular by the immune system, however Beyaz hopes he’s discovered a number of methods to outwit them.

Reference: “Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis” by Semir Beyaz, Charlie Chung, Haiwei Mou, Khristian E. Bauer-Rowe, Michael E. Xifaras, Ilgin Ergin, Lenka Dohnalova, Moshe Biton, Karthik Shekhar, Onur Eskiocak, Katherine Papciak, Kadir Ozler, Mohammad Almeqdadi, Brian Yueh, Miriam Fein, Damodaran Annamalai, Eider Valle-Encinas, Aysegul Erdemir, Karoline Dogum, Vyom Shah, Aybuke Alici-Garipcan, Hannah V. Meyer, Deniz M.Özata, Eran Elinav, Alper Kucukural, Pawan Kumar, Jeremy P. Mc Aleer, James G. Fox, Christoph A. Thaiss, Aviv Regev, Jatin Roper, Stuart H. Orkin and Ömer H. Yilmaz, 15 September 2021, Cell Stem Cell.
DOI: 10.1016/j.stem.2021.08.007

Funding: Nationwide Cancer Institute, Oliver S. and Jennie R. Donaldson Charitable Belief, Mathers Basis, STARR Cancer Consortium, Mark Basis For Cancer Analysis, Nationwide Institutes of Well being, Massachusetts Institute of Know-how Stem Cell Initiative, Pew Basis, Howard Hughes Medical Institute, American Affiliation of Immunologists Profession Reentry Fellowship
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