Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.
In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a pre-clinical mouse model of orthotopic PDAC with multiple exercise interventions. We demonstrated that gut microbiome differences between Tac and Jax result in differential exercise capacity with an intensity- dependent effect of exercise on tumor infiltrating immune cells.
We interrogated tumor stromal composition changes with exercise and observed a gut microbiome dependent reduction in alpha smooth muscle actin (αSMA+) cells and Il6 expressing inflammatory cancer associated fibroblasts (iCAFs). Similar analysis of tumors from patients in the PancFit trial demonstrated an exercise induced reduction in αSMA+ cells. We subsequently identified Cholic Acid (CA), a microbial bile acid that was increased in both patients and murine models with exercise, as a likely mediator of exercise induced reduction in iCAFs. Consistent with these findings, patients that exercised more also exhibited fewer iCAFs and lower tumor IL6 gene expression, supporting a stromal remodeling effect of physical activity.
In conclusion, this project demonstrates the role of host-intrinsic differences in regulation of exercise capacity, exercise-induced immune cell infiltration and activation, tumor growth, and stromal composition. Future work will evaluate the role of microbial metabolites such as CA as a biomarker of anti-tumor effect of exercise for patients with PDAC and as therapy for stromal remodeling to improve patient outcomes.
","abstract_html":"<p>Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.</p> <p>In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a pre-clinical mouse model of orthotopic PDAC with multiple exercise interventions. We demonstrated that gut microbiome differences between Tac and Jax result in differential exercise capacity with an intensity- dependent effect of exercise on tumor infiltrating immune cells.</p> <p>We interrogated tumor stromal composition changes with exercise and observed a gut microbiome dependent reduction in alpha smooth muscle actin (αSMA<sup>+</sup>) cells and <em>Il6</em> expressing inflammatory cancer associated fibroblasts (iCAFs). Similar analysis of tumors from patients in the PancFit trial demonstrated an exercise induced reduction in αSMA<sup>+</sup> cells. We subsequently identified Cholic Acid (CA), a microbial bile acid that was increased in both patients and murine models with exercise, as a likely mediator of exercise induced reduction in iCAFs. Consistent with these findings, patients that exercised more also exhibited fewer iCAFs and lower tumor <em>IL6</em> gene expression, supporting a stromal remodeling effect of physical activity.</p> <p>In conclusion, this project demonstrates the role of host-intrinsic differences in regulation of exercise capacity, exercise-induced immune cell infiltration and activation, tumor growth, and stromal composition. Future work will evaluate the role of microbial metabolites such as CA as a biomarker of anti-tumor effect of exercise for patients with PDAC and as therapy for stromal remodeling to improve patient outcomes.</p>","abstract_has_math":false,"creators":["Pareek, Sumedha","Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.
In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a pre-clinical mouse model of orthotopic PDAC with multiple exercise interventions. We demonstrated that gut microbiome differences between Tac and Jax result in differential exercise capacity with an intensity- dependent effect of exercise on tumor infiltrating immune cells.
We interrogated tumor stromal composition changes with exercise and observed a gut microbiome dependent reduction in alpha smooth muscle actin (αSMA+) cells and Il6 expressing inflammatory cancer associated fibroblasts (iCAFs). Similar analysis of tumors from patients in the PancFit trial demonstrated an exercise induced reduction in αSMA+ cells. We subsequently identified Cholic Acid (CA), a microbial bile acid that was increased in both patients and murine models with exercise, as a likely mediator of exercise induced reduction in iCAFs. Consistent with these findings, patients that exercised more also exhibited fewer iCAFs and lower tumor IL6 gene expression, supporting a stromal remodeling effect of physical activity.
In conclusion, this project demonstrates the role of host-intrinsic differences in regulation of exercise capacity, exercise-induced immune cell infiltration and activation, tumor growth, and stromal composition. Future work will evaluate the role of microbial metabolites such as CA as a biomarker of anti-tumor effect of exercise for patients with PDAC and as therapy for stromal remodeling to improve patient outcomes.
"]},{"key":"dc:title","label":"Title","values":["Host-intrinsic factors determine anti-tumor efficacy of exercise in pancreatic ductal adenocarcinoma"]}]}],"canonical_facts":{"dc:contributor":["Keri Schadler","Florencia McAllister","Seyed Javad Moghaddam"],"dc:creator":["Pareek, Sumedha","Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.
In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a pre-clinical mouse model of orthotopic PDAC with multiple exercise interventions. We demonstrated that gut microbiome differences between Tac and Jax result in differential exercise capacity with an intensity- dependent effect of exercise on tumor infiltrating immune cells.
We interrogated tumor stromal composition changes with exercise and observed a gut microbiome dependent reduction in alpha smooth muscle actin (αSMA+) cells and Il6 expressing inflammatory cancer associated fibroblasts (iCAFs). Similar analysis of tumors from patients in the PancFit trial demonstrated an exercise induced reduction in αSMA+ cells. We subsequently identified Cholic Acid (CA), a microbial bile acid that was increased in both patients and murine models with exercise, as a likely mediator of exercise induced reduction in iCAFs. Consistent with these findings, patients that exercised more also exhibited fewer iCAFs and lower tumor IL6 gene expression, supporting a stromal remodeling effect of physical activity.
In conclusion, this project demonstrates the role of host-intrinsic differences in regulation of exercise capacity, exercise-induced immune cell infiltration and activation, tumor growth, and stromal composition. Future work will evaluate the role of microbial metabolites such as CA as a biomarker of anti-tumor effect of exercise for patients with PDAC and as therapy for stromal remodeling to improve patient outcomes.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1501"],"dc:subject":["PDAC","Exercise","Pancreatic Cancer","CAFs","Tumor Infiltrating Immune Cells","Stroma","Exercise Capacity","Gut Microbiome","Cholic Acid","IL6","Animal Experimentation and Research","Behavior and Behavior Mechanisms","Biology","Cancer Biology","Exercise Science","Immunity","Medical Immunology"],"dc:title":["Host-intrinsic factors determine anti-tumor efficacy of exercise in pancreatic ductal adenocarcinoma"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:47Z"}