학술논문
Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Document Type
Academic Journal
Author
Deng N; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Reyes-Uribe L; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Fahrmann JF; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Thoman WS; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Munsell MF; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Dennison JB; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Murage E; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Wu R; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Hawk ET; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Thirumurthi S; Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Lynch PM; Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Dieli-Conwright CM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Lazar AJ; Department of Behavioral Science, The University of Texas MD Anderson, Houston, Texas.; Department of Genomic Medicine, The University of Texas MD Anderson, Houston, Texas.; Jindal S; The Immunotherapy Platform, The University of Texas MD Anderson, Houston, Texas.; Chu K; The Immunotherapy Platform, The University of Texas MD Anderson, Houston, Texas.; Chelvanambi M; Department of Surgical Oncology, The University of Texas MD Anderson, Houston, Texas.; Basen-Engquist K; Department of Behavioral Science, The University of Texas MD Anderson, Houston, Texas.; Li Y; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Wargo JA; Department of Genomic Medicine, The University of Texas MD Anderson, Houston, Texas.; Department of Surgical Oncology, The University of Texas MD Anderson, Houston, Texas.; McAllister F; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Immunology, The University of Texas MD Anderson, Houston, Texas.; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson, Houston, Texas.; Allison JP; The Immunotherapy Platform, The University of Texas MD Anderson, Houston, Texas.; Department of Immunology, The University of Texas MD Anderson, Houston, Texas.; Sharma P; The Immunotherapy Platform, The University of Texas MD Anderson, Houston, Texas.; Department of Immunology, The University of Texas MD Anderson, Houston, Texas.; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, Texas.; Sinha KM; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Hanash S; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Gilchrist SC; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Cardiology, The University of Texas MD Anderson, Houston, Texas.; Vilar E; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson, Houston, Texas.
Source
Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: 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.
Patients and Methods: 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.
Results: 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.
Conclusions: 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.
(©2023 The Authors; Published by the American Association for Cancer Research.)
Patients and Methods: 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.
Results: 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.
Conclusions: 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.
(©2023 The Authors; Published by the American Association for Cancer Research.)