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

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.