Senescent white blood cells in colorectal carcinoma patients

Abstract

Colorectal cancer (CRC) and ageing can contribute to changes in immune cells including immuno-senescence. The objectives of the study were to determine if the senescence marker (p16INK4A) was expressed more at higher levels in peripheral white blood cells in CRC compared to age-matched healthy controls. Another aim was to determine the phenotypic changes of T cells, NK cells and monocytes during ageing and CRC in case-control studies. Cases were patients with CRC and controls were matched with cases based on age. Peripheral immune cells were analysed for p16INK4A using immunofluorescence and immunophenotypes were determined with flow cytometry. Correlation studies with age and clinical data were performed. Increased p16INK4A expression in peripheral immune cells had 78% sensitivity and 71% specificity. T lymphocytes and monocytes had increased intensity of p16INK4A. The proportion of monocytes increased alongside a reduction of lymphocytes, indicating myeloid skew in CRC and aging. Most T cells subsets decreased during ageing except helper T cells, and the reverse patterns were observed in CRC. NK cells expanded during ageing but showed a decreased trend in CRC. Immunophenotypes in monocytes were similar in ageing and CRC: classical monocytes decreased while intermediate monocytes and non-classical monocytes both increased. Most of the increased T cells and monocytes were senescent-like cells with immunosuppressive phenotypes in CRC. The potential of p16INK4A expression and CD4+ monocytes as disease-related and/or age-related biomarkers is discussed.