Abstract
Aging is an important determinant of patient outcome in colorectal cancer (CRC), and more than 90% of diagnoses occur in people aged over fifty. During aging, thymic involution results in remodelling of the T cell compartment to produce fewer naïve T cells with a compensatory expansion of memory T cells (immune senescence). Additionally, T cell populations that control inflammation (regulatory T cells, Tregs) accumulate with age; however, their suppressive capacity declines, leading to chronic inflammation.
The aging immune system’s impact on CRC is largely unknown. A lack of age-matched controls mean it is not understood whether known immune implications in CRC develop due to the presence of cancer, or during natural aging. Changes in the immune system with age may contribute to the development of cancer, so identifying differences between the young and aged immune system is important.
I optimised a 25-parameter spectral flow cytometry panel comprising surface markers, transcription factors and cytokines for comprehensive immune profiling, focussed on T cells. A cohort of young, healthy donors (n = 10), a cohort of CRC patients (n = 3), and an age-matched non-CRC cohort (n = 45) were analysed for circulating immune populations using Kruskal-Wallis and Dunn’s statistical tests. The young healthy cohort had a significantly higher proportion of CD4+ T cells expressing interleukin-2 (IL-2), compared to the aged cohort (p < 0.0001). There was no statistically significant difference in the frequency of CD4+ Tregs between the young and aged cohorts (p = 0.1454), but a significantly higher percentage of Tregs in the CRC cohort compared to the young healthy cohort (p = 0.0049). The frequency of CD4+ interleukin-17 (IL-17)+ T cells in the aged cohort was significantly lower than in the CRC cohort (p = 0.0084) and the young healthy cohort (p = 0.0248).
IL-2+ T cells represent an active phenotype that promotes T cell proliferation, often associated with good prognosis in CRC. Tregs are thought to contribute to poor prognosis by suppressing anti-tumour T cell responses, but have also been linked to better patient outcomes, although this mechanism is not understood. This preliminary data shows the heterogeneity of the immune response in different age groups and provides insight into populations and functions of cells present in aged individuals with and without CRC; and could be used to inform patient outcomes.