Associations between calcium intake and T cell infiltration in colorectal tumours.

Journal: Cancer prevention research (Philadelphia, Pa.)
Published Date: May 15, 2025

Abstract

Higher T cell infiltration in colorectal tumours has been associated with better prognosis. Evidence indicates that calcium signalling is essential for T cells functioning. However, as it is unknown whether calcium intake influences T cell infiltration, we investigated the association of calcium intake with T cell subsets in the tumour microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumour infiltrating T cells and calcium intake was available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, DAPI). Associations between pre-diagnostic calcium intake and densities of non-overlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double negative T cells density in the epithelial (OR 1.57; 95% CI 1.13-2.24) and stromal (OR 1.24; 95%CI 1.06-1.45) tumour tissue area. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double negative T cells in the epithelial and stromal tumour tissue area, but not with infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumour immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.

Authors

  • Evertine Wesselink
    Wageningen University & Research, Wageningen, Netherlands.
  • Claire E Thomas
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Yasutoshi Takashima
    Brigham and Women's Hospital, Boston, MA, United States.
  • Hiroki Mizuno
    Brigham and Women's Hospital, Boston, MA, United States.
  • Daniel D Buchanan
    University of Melbourne, Parkville, Victoria, Australia.
  • Conghui Qu
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Li Hsu
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Andressa Dias Costa
    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Satoko Ugai
    Harvard University, Boston, MA, United States.
  • Yuxue Zhong
    Brigham and Women's Hospital, Cambridge, United States.
  • Jeroen R Huyghe
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Sushma Thomas
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Steven Gallinger
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Robert C Grant
    Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Loïc Le Marchand
    University of Hawaii Cancer Center, Honolulu, Hawaii, United States.
  • Yohei Masugi
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
  • Fränzel Jb van Duijnhoven
    Wageningen University & Research, Wageningen, Netherlands.
  • Tomotaka Ugai
    Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Shuji Ogino
    Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Jonathan A Nowak
    Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. janowak@bwh.harvard.edu.
  • Ulrike Peters
    Fred Hutchinson Cancer Center, Seattle, WA, United States.
  • Amanda I Phipps
    Department of Epidemiology, University of Washington, Seattle.

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