Exercise Modulates Microbial Metabolites and Induces Stromal Remodeling in Pancreatic Cancer
Year: 2026
Type: article
Abstract: Exercise induces a variety of changes in the tumor microenvironment, with beneficial effects in several tumor types. However, a better understanding of the clinical effects of exercise and mediating mechanisms is needed to maximize the utility of exercise for patients. In this study, we analyzed tumors from patients with pancreatic ductal adenocarcinoma (PDAC) in the PancFit trial and identified an exercise-induced reduction in cells expressing α-smooth muscle actin (αSMA). Interrogation of changes in tumor stromal composition with exercise in a murine PDAC model revealed a microbially influenced reduction in αSMA+ cells and Il6-expressing inflammatory cancer-associated fibroblasts (iCAF). Cholic acid, a microbial bile acid, was increased in both patients and murine models with exercise, as a potential mediator of exercise-induced reduction in iCAFs. Consistent with these findings, patients that exercised more also exhibited fewer iCAFs and lower tumor IL6 expression, supporting a stromal remodeling effect of physical activity. In summary, this study demonstrates that the antitumor effect of exercise includes stromal remodeling, which is affected by microbial metabolites. SIGNIFICANCE: Exercise-induced changes in cancer associated fibroblasts vary with microbiome composition, which may explain the heterogeneity in tumor responses to exercise and could guide future exercise trials in cancer patients.
Source: Cancer Research
Authors: Sumedha Pareek, Robin D. Wright, Riccardo Ballarò, Cayla Xue, Thais F. Bartelli, Vidhi Chandra, Le Li, Justina Ortiz, Truong Lam, Hetal Patel, Jonghae Lee, Pradeep Shrestha, Hannah Savage, Olivereen Le Roux, Haoyue Liu, Tamara Vallejo-Schmidt, Ryan De Maleki, Vasanta Putluri, Nagireddy Putluri, Joseph F. Petrosino, Jared K. Burks, Javier A. Gomez, Jlenia Guarnerio, Matthew H.G. Katz, An Ngo-Huang, Laura R. Prakash, Nathan H. Parker, Maria Q.B. Petzel, Lin Tan, Seyda Baydogan, Florencia McAllister, Keri L. Schadler
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Modulating the Gut- Tumor Microbial Axis to Reverse Pancreatic Cancer Immunosuooression, G2955680221, G418187648, G4182736573, G4204617519, Proteomics and Metabolomics Core Facility, G5108285509, G7663504393, Role of S1PR1 in Exercise-Induced Tumor Vascular Remodeling, G9000841871, G9000845188, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W7203827265
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