Mayo Clinic Symposium on Regenerative Medicine & Surgery 2021 recap

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The future of regenerative medicine is bright," declared Julie Allickson, Ph.D., the Michael S. and Mary Sue Shannon Director of Mayo Clinic's Center for Regenerative Medicine, as she delivered the opening keynote address of the Mayo Clinic Symposium on Regenerative Medicine & Surgery 2021. Dr. Allickson is the Otto Bremer Trust Director, Biomanufacturing and Product Development, Center for Regenerative Medicine

Dr. Allickson highlighted ways regenerative medicine is on the threshold of delivering new therapeutic options to patients. She pointed to the first in-vivo gene editing clinical trial in the U.S. using the CRISPR Cas-9 editing technology and the potential of expanding chimeric antigen receptor-T cell therapy (CAR-T cell therapy) beyond leukemia, lymphoma and multiple myeloma. From advancements in bioengineered organ research to the latest innovations in tissue engineering and 3D printing, regenerative medicine is on the cusp of transforming health care.

Throughout the four-day symposium, experts at Mayo Clinic and around the world shared regenerative medicine applications to aging, musculoskeletal conditions, lung diseases, organ transplantation and cancer.

Colorectal Cancer Model Finds Out-of-Tune T Cells

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When it comes to the immune system, attention seems to focus on its protection. But equally important is how the unleashed immune response becomes a threat. In two recent Nature Immunology papers, scientists provide insight into how colorectal cancer rewires regulatory T cells, or Treg cells, to promote tumor growth. In that setting, Treg cells switch from suppressing to promoting inflammation, fueling tumor growth. Simultaneously, they protect tumors from attack by T cells. Regulatory T cells in the colon interact with microbiota and immune cells to produce a healthy level of inflammation that protects against infection. These Treg cells are "tuned" to suppress the immune response by the protein FOXP3, and "fine-tuned" by the proteins ROR-gamma-T, beta-catenin and TCF-1. But colon tumors secrete biological mediators that alter the gut microbiota and properties of Treg cells. Tumor growth causes elevated expression of beta-catenin and lower expression of TCF-1 in Treg cells. In turn, while this makes Treg cells unable to control inflammation, they are better at suppressing T-cells. Image created with BioRender.

Khashayarsha Khazaie, Ph.D., a Mayo Clinic scientist; Fotini Gounari, Ph.D., a scientist at The University of Chicago; and Majid Kazemian, Ph.D., a Purdue University researcher, identified key molecules that direct these changes in regulatory T cell functions in colorectal cancer. This knowledge opens a new window to understand how cancer compromises immunity to its advantage, paving the path to better-targeted cancer prevention and treatment.Out-of-Tune Immune Cells

"The general notion is that the job of Treg cells is to suppress immune responses. But they actually have many different functions and can use these in various combinations under different circumstances in the body," says Dr. Khazaie. "And one such exact circumstance for me is cancer. A single protein called FOXP3 broadly dictates Treg suppressive functions, while others, including ROR-gamma-T, beta-catenin and TCF-1, fine-tune them."

It is a win-win situation for colon cancer