Associations between Calcium Intake and T-cell Infiltration in Colorectal Tumors

Higher T-cell infiltration in colorectal tumors has been associated with better prognosis. Evidence indicates that calcium signaling is essential for T-cell 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 tumor microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumor-infiltrating T cells and calcium intake were 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, and di-(4-amidinophenyl)-1H-indole-6-carboxamidine). Associations between prediagnostic calcium intake and densities of nonoverlapping 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-cell density in the epithelial (OR, 1.57; 95% confidence interval, 1.13-2.24) and stromal (OR, 1.24; 95% confidence interval, 1.06-1.45) tumor tissue areas. 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 tumor tissue areas but not with the infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumor-immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.

Our research contributes to the understanding of how diet could influence immune cell infiltration in and around the tumor. Understanding which factors influence antitumor immune responses is of importance in the prevention of cancer recurrence and/or progression.