American Association for Cancer Research
ccr-23-0088_supplementary_table_s7_suppts7.xlsx (24.43 kB)

Supplementary Table S7 from Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome

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posted on 2023-11-01, 07:20 authored by Nan Deng, Laura Reyes-Uribe, Johannes F. Fahrmann, Whittney S. Thoman, Mark F. Munsell, Jennifer B. Dennison, Eunice Murage, Ranran Wu, Ernest T. Hawk, Selvi Thirumurthi, Patrick M. Lynch, Christina M. Dieli-Conwright, Alexander J. Lazar, Sonali Jindal, Khoi Chu, Manoj Chelvanambi, Karen Basen-Engquist, Yisheng Li, Jennifer A. Wargo, Florencia McAllister, James P. Allison, Padmanee Sharma, Krishna M. Sinha, Samir Hanash, Susan C. Gilchrist, Eduardo Vilar

Table S7. Results of in silico deconvolution of immune cell types using CIBERSORT.


National Cancer Institute (NCI)

United States Department of Health and Human Services

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Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

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