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Density of CD3+ and CD8+ cells in the microenvironment of colorectal cancer according to pre-diagnostic physical activity
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0002-9045-6946
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-4688-8952
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0002-8958-975X
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2021 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, no 12, p. 2317-2326Article in journal (Refereed) Published
Abstract [en]

Introduction: Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients.

Method: The study setting was a northern Swedish population-based cohort, including 109792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3+ and CD8+ cytotoxic T-cells by immunohistochemistry. Odds ratios for associations between self-reported, pre-diagnostic recreational physical activity and immune-cell infiltration were estimated by ordinal logistic regression.

Results: Recreational physical activity >3 times per week was associated with a higher density of CD8+ T-cells in the tumor front and center compared to participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI 1.21-6.35) and 2.85 (95% CI 1.28-6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3 no clear associations were found.

Conclusion: Physical activity may promote the infiltration of CD8+ immune cells in the tumor microenvironment of colorectal cancer.

Impact: The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.

Place, publisher, year, edition, pages
American Association for Cancer Research (AACR) , 2021. Vol. 30, no 12, p. 2317-2326
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-188712DOI: 10.1158/1055-9965.EPI-21-0508ISI: 000728256100001PubMedID: 34607838Scopus ID: 2-s2.0-85121664424OAI: oai:DiVA.org:umu-188712DiVA, id: diva2:1604380
Funder
Swedish Cancer Society, 2017/581Region Västerbotten, RV‐939032Visare Norr, 929704Cancerforskningsfonden i NorrlandAvailable from: 2021-10-19 Created: 2021-10-19 Last updated: 2025-09-08Bibliographically approved
In thesis
1. Aspects of pre-diagnostic physical activity in colorectal cancer
Open this publication in new window or tab >>Aspects of pre-diagnostic physical activity in colorectal cancer
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Aspekter av pre-diagnostisk fysisk aktivitet vid tjock- och ändtarmscancer
Abstract [en]

Background: Pre-diagnostic physical activity may lower the risk for developing colon cancer and is potentially associatedwith improved prognosis when diagnosed with colorectal cancer. Body composition and immune cell infiltration in the tumour microenvironment are also associated with prognosis in colorectal cancer. The physical activity guidelines are the same in colorectal cancer patients as in the healthy population and the national health care programme for colorectal cancer in Sweden recommends individualised support for physical activity to all patients.

Aims: The overall aim of this thesis was to evaluate pre-diagnostic physical activity, assessed using self-reported questionnaire, from physical tests, by using an accelerometer, using interviews and its relationship with colorectal cancer with regard to immune cell infiltration of the tumour, body composition, and the patient’s own experiences.

Results: Study I: Pre-diagnostic physical exercise more than three times a week was associated with increased numbers of cytotoxic T cells in the tumour front (OR 2.91, 95% CI 1.25-6.75) and centre (OR 2.92, 95% CI1.31-6.50)

Study II: Low pre-diagnostic physical exercise was not associated with sarcopenia, i.e. low muscle mass (OR1.37, 95% CI 0.86-2.19) nor myosteatosis, i.e. low muscle quality (OR 0.95, 95% CI 0.59-1.51) at the time of colorectal cancer diagnosis

Study III: After adjusting for multiple testing no significant results were seen in either the descriptive statistics or in the logistic regression model adjusted for age and sex.

Study IV: Various experiences were expressed towards physical activity described in three main categories “I’ll fight the cancer and come out stronger”; “the diagnosis makes no difference”; and “the cancer is an obstacle for physical activity”.

Conclusions: Self-reported physical exercise may be associated with increased numbers of cytotoxic T cells in the microenvironment of colorectal cancer. However, this was neither confirmed nor rejected when assessing physical activity and fitness more objectively in a smaller cohort. Little physical exercise in middle age was not associated with sarcopenia or myosteatosis at the time of colorectal cancer diagnosis but when present together, cancer-specific mortality risk was increased. Physically active individuals have a wide spectrum of attitudes and experiences toward physical activity when diagnosed with colon cancer.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2025. p. 89
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2369
Keywords
Colorectal cancer, Immune cell infiltration, Myosteatosis, Physical activity, Sarcopenia
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:umu:diva-243999 (URN)978-91-8070-732-9 (ISBN)978-91-8070-733-6 (ISBN)
Public defence
2025-10-03, Aulan, hiss 8, vån 1, Sundsvalls Sjukhus, Sundsvall, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2025-09-12 Created: 2025-09-08 Last updated: 2025-09-12Bibliographically approved

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Renman, DavidGylling, BjörnVidman, LindaBodén, StinaStrigård, KarinPalmqvist, RichardHarlid, SophiaGunnarsson, Ulfvan Guelpen, Bethany

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Renman, DavidGylling, BjörnVidman, LindaBodén, StinaStrigård, KarinPalmqvist, RichardHarlid, SophiaGunnarsson, Ulfvan Guelpen, Bethany
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SurgeryPathologyOncologyWallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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