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Association of objectively assessed physical activity with immune cell infiltration of the tumor microenvironment in non-metastatic colon cancer
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0002-9045-6946
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-1901-8011
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0002-3806-2114
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Both physical activity and immune cell infiltration of the tumor microenvironment are associated with improved prognosis in colon cancer. There is also evidence that physical activity may mobilize immune cells against colon tumors. One possible mechanism behind the positive effect of physical activity on colon cancer prognosis could thus be increased immune cell infiltration of the tumor microenvironment. There are few previous studies examining this association, and none has included an objective assessment of physical activity and fitness.

Methods: This was a cohort study on 69 patients diagnosed with colon cancer stages I-III, all eligible for curative surgery, and with no previous treatment. Prior to surgery, the participants underwent physical tests, dual-energy X-ray absorptiometry, and wore an accelerometer to quantify their physical activity and physical fitness. Tumor infiltration by cytotoxic T cells, T-helper 1 cells, regulatory T cells, B cells, and macrophages was objectively assessed with multispectral quantitative automated pathology imaging. Odds ratios for associations between physical activity and immune cell infiltration were estimated by logistic regression.

Results: A higher number of repetitions in the 30-second sit-to-stand test was associated with a lower density of T-helper 1 cells in the stromal compartment of the tumor, in the model adjusted for age and sex. When correcting for multiple testing the association was considered non-significant. No other significant association was seen for any of the physical tests or immune cell types in the multivariable logistic regression models.

Conclusions: No consistent evidence was found to support the hypothesis of an association between physical activity or fitness and increased immune cell tumor infiltration in colon cancer.

Trial registration: This study was registered at clinicaltrials.gov (ID: NCT03947840).

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-243998OAI: oai:DiVA.org:umu-243998DiVA, id: diva2:1995951
Available from: 2025-09-08 Created: 2025-09-08 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, DavidEdin, SofiaGunnarsson, UlfBlind, NiillasStrigård, KarinPalmqvist, Richard

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