Exercise & Training

Association of objectively assessed physical activity with immune cell infiltration of the tumor microenvironment in non-metastatic colon cancer.

TL;DR

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.

Key Findings

A higher number of repetitions in the 30-second sit-to-stand test was associated with lower density of T-helper 1 cells in the stromal compartment of the tumor after adjustment for age and sex.

  • This association was the only statistically notable finding across all physical tests and immune cell types examined
  • The association was considered non-significant after correcting for multiple testing
  • The direction of the association was inverse, meaning better physical performance correlated with lower, not higher, immune cell density
  • The model was adjusted for age and sex

No significant associations were found between objectively measured physical activity and tumor infiltration by cytotoxic T cells, regulatory T cells, B cells, or macrophages.

  • Immune cell infiltration was assessed using multispectral quantitative automated pathology imaging
  • Five immune cell types were evaluated: cytotoxic T cells, T-helper 1 cells, regulatory T cells, B cells, and macrophages
  • No consistent pattern of association emerged across any immune cell type or tumor compartment
  • Physical activity was measured objectively via accelerometer worn prior to surgery

The study enrolled 69 patients with non-metastatic colon cancer (stages I-III) from the PACOS prospective cohort who were eligible for curative surgery and had received no previous treatment.

  • The cohort was part of the Physical Activity and its impact on COlon cancer Surgery (PACOS) prospective cohort
  • All participants underwent physical tests, dual-energy X-ray absorptiometry (DEXA), and wore an accelerometer prior to surgery
  • The study was registered at clinicaltrials.gov with ID NCT03947840, registration date 2019-05-19
  • Participants had no previous treatment for colon cancer prior to enrollment

Odds ratios were used to estimate associations between physical activity measures and immune cell infiltration, but no consistent evidence supported the hypothesized positive relationship.

  • Multiple physical fitness assessments were included: the 30-second sit-to-stand test, physical tests, and accelerometer-measured activity
  • Body composition was assessed using dual-energy X-ray absorptiometry
  • Tumor immune cell density was assessed in the tumor microenvironment using multispectral quantitative automated pathology imaging
  • No physical activity or fitness measure was significantly associated with increased immune cell infiltration after correction for multiple testing

The study is the first to examine the association between objectively assessed physical activity and immune cell tumor infiltration in colon cancer.

  • Prior studies in this area had not included objective assessment of physical activity
  • The hypothesis under investigation was that physical activity may mobilize immune cells against colon tumors as a mechanism behind improved prognosis
  • Both physical activity and immune cell infiltration of the tumor microenvironment are independently associated with improved prognosis in colon cancer
  • The current study found no evidence linking these two factors in the pre-surgical setting

What This Means

This research studied whether physically active colon cancer patients have more immune cells attacking their tumors. The idea was that exercise might help the immune system fight cancer by sending more immune cells into the tumor environment — a possible explanation for why physically active cancer patients tend to have better outcomes. The study followed 69 patients with early-to-middle stage colon cancer who wore activity trackers and underwent fitness tests before their surgery, then examined their tumor tissue for five types of immune cells using advanced imaging technology. The study found no consistent evidence that more physically active or fitter patients had greater immune cell infiltration in their tumors. The only notable finding was that patients who performed better on a sit-to-stand fitness test had slightly fewer of one type of immune cell (T-helper 1 cells) in their tumors, but this result disappeared after accounting for the fact that many different associations were tested simultaneously, making it likely a chance finding. This research suggests that the well-known survival benefit of physical activity in colon cancer patients may not work through the specific mechanism of increasing immune cell infiltration of tumors — at least not in a way detectable at the time of surgery. The authors note this is the first study to use objective physical activity measurement (an accelerometer) rather than self-reported activity, making it a more rigorous test of this hypothesis. Future research may need to look at other biological pathways or different timing of physical activity measurement to understand how exercise improves colon cancer outcomes.

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Citation

Renman D, Edin S, Gunnarsson U, Blind N, Strigård K, Palmqvist R. (2026). Association of objectively assessed physical activity with immune cell infiltration of the tumor microenvironment in non-metastatic colon cancer.. International journal of colorectal disease. https://doi.org/10.1007/s00384-026-05232-5