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Discovering the Role of the Gut Microbiome on Cancer Immunotherapy

The trillions of bacteria, viruses, and fungi living in our gut, collectively known as the gut microbiome, create a mini-ecosystem that plays a significant role in our health. Microorganisms signal other molecules in our body and influence physiological, metabolic, hormone, and immune function.

Recent research suggests that the gut microbiome has a dramatic effect on the immune system’s ability to fight different cancers. Last year, three separate studies published in Science showed that the gut microbiome remarkably influences how well a cancer patient responds to cancer immunotherapy.

Based on these findings, Professor Hyun Jung Kim is using his innovative gut-on-a-chip model to learn more.

Kim and his Biomimetic Microengineering (BioME) lab have received the Cancer Research Institute’s Technology Impact Award, which provides $200,000 of seed funding to find out how the gut microbiome orchestrates the human immune system’s ability to treat cancer.

In collaboration with Dr. Gail Eckhardt and Dr. Declan Fleming of the Dell Medical School’s LIVESTRONG Cancer Institutes, Woojung Shin, a third-year graduate student in the BioME lab, will isolate colonic biopsies from both colorectal cancer and healthy human patients. Shin will then grow these stem cell-containing tissue fragments to form 3D organoids, which are miniature models of the human gut. Because these organoids are made from biopsied tissue, the models represent the genetic background of the donor patients. With these patient-specific organoid cells, Shin will microengineer a colon cancer chip to form a 3D tissue interface that mimics the real human colon.

discovering the role of the gut microbiome on cancer immunotherapy

A cross section view of an organoid created from healthy human colon cells. The red represents the cytoskeleton of the cells and the cyan is the nuclei of the colon-derived organoid. Researchers will use these organoid models to study how gut bacteria influences the human immune system's ability to fight cancer.

“Organoid cultures provide a wonderful technical advance because they provide more effective and accurate ways to study the heterogeneity of colorectal cancer in individual patients,” says Kim. “Combining organoid cultures with our biomimetic organ-on-a-chip device, will allow us to learn about the host-microbiome crosstalk that may disrupt the immune checkpoint repertoire.”

The colon cancer chip platform is a more accurate testing option than an animal model. First, animal models do not accurately predict human physiology. The gut microbiome in a mouse model is less than 15 percent similar to that of a human’s gut. That dissimilarity is one reason that drugs metabolize differently and why many clinical trials fail. Finally, it is impossible to uncouple complex interactions and independently recouple each contributing factor one-at-a-time in animal models, whereas using the colon cancer chip will help researchers identify the independent role of the gut microbiome on altering the checkpoint repertoires in immune and epithelial cells.

“Using human cell-based models will help us learn how we may be able to improve treatment of colorectal cancer patients by balancing the healthy “keystone gut microbiome,” which is essential in harnessing the power of our own immune system’s ability to fight disease,” Kim says.