Marco Donia, Research Group Leader of the TIL group at CCIT (Center for Cancer Immune Therapy) and Professor at the University of Copenhagen, shared a post on LinkedIn about a paper by Catherine M. Phelps et al. published in Cell:
“Exercise-Microbiota-Immunity: Mechanistic insights with clinical potential in cancer.
This preclinical study reveals how exercise enhances immune checkpoint inhibitor (ICI) efficacy in melanoma through a gut microbiota-dependent mechanism.
Exercise stimulates microbial one-carbon metabolism, leading to increased production of formate – a simple gut-derived molecule (HCOO⁻) that acts as a metabolic signal. Formate activates the Nrf2 pathway in cytotoxic CD8⁺ T cells, strengthening antitumor immune responses and improving immunotherapy outcomes.
Key findings
- Exercise elevates microbiota-derived formate, enhancing cytotoxic CD8⁺ T cell activity.
- Formate is both required and sufficient for the tumor-suppressive effects of exercise.
- The Nrf2 pathway mediates formate-induced T cell activation.
- Mice receiving formate-rich microbiota or oral formate show improved ICI response and tumor control.
Clinical implications
- Suggests formate may act as a metabolic enhancer to improve immunotherapy efficacy.
- Supports structured exercise as a biological co-treatment in oncology care.
- Highlights potential microbiota-metabolite biomarkers to identify patients who may benefit most from an exercise-immune synergy.
Take-home message
- Exercise may not just support cancer therapy – it may actively drive it.
- This study positions the gut microbiota as a modifiable link between lifestyle, metabolism, and immune activation, advancing the concept of precision exercise-oncology.
Great work from the team of Marlies Meisel․
Post by Louise Lang Lehrskov from Afdeling for Kræftbehandling, Herlev og Gentofte Hospital, a real expert in exercise-oncology.”
Title: Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity, promoting immunotherapy efficacy
Authors: Catherine M. Phelps, Nathaniel B. Willis, Tingting Duan, Amanda H. Lee, Yue Zhang, Daphne M. Rodriguez J, Surya P. Pandey, Colin R. Laughlin, Aaron B.I. Rosen, Alex C. McPherson, Jake H. Shapira, Simran K. Randhawa, Lee Hedden, Tanner G. Richie, Hallie M. Wiechman, Mackenzie J. Bender, Ina Nemet, Patrick A. Zöhrer, Rachel A. Gottschalk, Kathryn H. Schmitz, Steven J. Mullett, Stacy L. Gelhaus, Diwakar Davar, Hassane M. Zarour, Reinhard Hinterleitner, Thomas Mossington, Jonathan H. Badger, Richard R. Rodrigues, John A. McCulloch, Sonny T.M. Lee, Karl-Heinz Wagner, Maria G. Winter, Sebastian E. Winter, Jishnu Das, Joseph F. Pierre, Giorgio Trinchieri, and Marlies Meisel
You can read the Full Article in Cell.
More posts featuring Marco Donia.
