Physical Activity and Colorectal Cancer Prognosis According to Tumor-Infiltrating T Cells

Hideo Koh, Tsuyoshi Hamada, Mingyang Song, Li Liu, Yin Cao, Jonathan A. Nowak, Annacarolina da Silva, Tyler Twombly, Teppei Morikawa, Sun A. Kim, Yohei Masugi, Keisuke Kosumi, Yan Shi, Mancang Gu, Wanwan Li, Chunxia Du, Yang Chen, Wenbin Li, Hongli Liu, Chenxi LiKana Wu, Katsuhiko Nosho, Kentaro Inamura, Akiko Hanyuda, Xuehong Zhang, Marios Giannakis, Andrew T. Chan, Charles S. Fuchs, Reiko Nishihara, Jeffrey A. Meyerhardt, Shuji Ogino

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Evidence suggests that high-level physical activity may potentially reduce cancer mortality through its immune enhancement effect. We therefore hypothesized that survival benefits associated with physical activity might be stronger in colorectal carcinomas with lower immune reaction at diagnosis. Methods: Using molecular pathological epidemiology databases of 470 colon and rectal carcinoma cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis physical activity in strata of densities of CD3þ cells, CD8þ cells, CD45RO (PTPRC)þ cells, or FOXP3þ cells in tumor tissue. Cox proportional hazards regression model was used to adjust for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, KRAS, BRAF, and PIK3CA mutations, and expression of CTNNB1 (beta-catenin), PTGS2 (cyclooxygenase-2), and IRS1. Results: The association of postdiagnosis physical activity with colorectal cancer-specific mortality differed by CD3þ cell density (Pinteraction < .001). Multivariable-adjusted colorectal cancer-specific mortality hazard ratios for a quartile-unit increase in physical activity were 0.56 (95% confidence interval = 0.38 to 0.83) among cases with the lowest quartile of CD3þ cell density compared with 1.14 (95% confidence interval = 0.79 to 1.65) in cases with the highest quartile. We observed no differential survival association of physical activity by densities of CD8þ cells, CD45ROþ cells, or FOXP3þ cells. Conclusions: The association between postdiagnosis physical activity and colorectal cancer survival appeared stronger for carcinomas with lower T cell infiltrates, suggesting an interactive effect of exercise and immunity on colorectal cancer progression.

Original languageEnglish
Article numberpky058
JournalJNCI Cancer Spectrum
Issue number4
Publication statusPublished - 2018 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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