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The Efficacy of Immune Checkpoint Inhibitors in Melanoma Through a Gut Microbiota – Mirrors of Medicine

Catherine Phelps/X

Aug 12, 2025, 10:34

The Efficacy of Immune Checkpoint Inhibitors in Melanoma Through a Gut Microbiota – Mirrors of Medicine

Mirrors of Medicine shared a post on X:

“Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity, promoting immunotherapy efficacy.

Study reveals that exercise enhances the efficacy of immune checkpoint inhibitors (ICIs) in melanoma through a gut microbiota–driven mechanism centered on the metabolite formate.

Exercise stimulates microbial one-carbon metabolism, increasing formate production, which is both necessary and sufficient to boost cytotoxic CD8+ T cell (Tc1) responses and improve ICI-mediated tumor control. Mechanistically, formate enhances Tc1 function via activation of the transcription factor Nrf2, playing a pivotal role in exercise’s antitumor effects.

Importantly, high formate–producing human gut microbiota similarly augments Tc1-mediated antitumor immunity, positioning microbiota-derived formate as both a functional driver of tumor suppression and a potential biomarker for predicting enhanced ICI responses.”

Title: Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy

Journal: Cell

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, Marlies Meisel

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Mirrors of Medicine

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Aaron B.I. Rosen Alex C. McPherson Amanda H. Lee cancer Catherine M. Phelps Colin R. Laughlin Daphne M. Rodriguez J Diwakar Davar Giorgio Trinchieri gut microbiota Hallie M. Wiechman Hassane M. Zarour ICIs Immune Checkpoint Inhibitors immunotherapy Ina Nemet Jake H. Shapira Jishnu Das John A. McCulloch Jonathan H. Badger Joseph F. Pierre Karl-Heinz Wagner Kathryn H Schmitz Lee Hedden Mackenzie J. Bender Maria G. Winter Marlies Meisel Melanoma Mirrors of Medicine Nathaniel B. Willis OncoDaily Oncology Patrick A. Zöhrer Rachel A. Gottschalk Reinhard Hinterleitner Richard R. Rodrigues Sebastian E. Winter Simran K. Randhawa Sonny T.M. Lee Stacy L. Gelhaus Steven J. Mullett Surya P. Pandey Tanner G. Richie Thomas Mossington Tingting Duan Yue Zhang

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