Abstract
Aging is one of the most important determinants of patient outcome in many cancers, especially colorectal cancer (CRC), where more than 90% of diagnoses occur in people aged over fifty. As we age, the function and composition of our immune system changes. In particular, 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). In addition, the T cell populations that normally control inflammation (regulatory T cells, (Tregs)) also accumulate with age; however, their suppressive capacity declines, creating a state of chronic inflammation. How the aging immune system interacts with CRC is still largely unknown. Due to a lack of age-matched control cohorts it is not understood whether previously discovered immune cells in CRC develop due to the presence of cancer itself or as a natural process during aging. Because changes in the immune system with age may contribute to the development of cancer, identifying immune differences between the young and aged immune system is important.
In this study I optimised a 25-parameter spectral flow cytometry panel comprising surface markers, transcription factors and cytokines to conduct comprehensive immune profiling of immune cells, focussed on T cells. A cohort of young, healthy donors, a cohort of CRC patients, and an age-matched non-CRC cohort were analysed for circulating immune populations. I found that 14.5% of cells from the CD4 T cell compartment in the young healthy cohort expressed IL-2, compared to 3.1% in the aged cohort which was significantly lower (p=<0.0001). I then investigated CD4+ Tregs and found no statistically significant difference in frequency between the young and aged cohorts (p=0.2730), but a significantly higher percentage of Tregs in the CRC cohort compared to the other cohorts (p=0.0010 (young) and p=0.0048 (aged)). The frequency of CD4+ IL-17+ T cells in the CRC cohort was significantly iihigher than the young and aged cohorts (4.9% compared to 0.57% p=<0.0001 (young)) and 0.9%; (p=<0.0001 (aged)). I compared unsupervised analysis with conventional flow analysis and found that high dimensional clustering did not identify any new immune cell populations. This study provides preliminary data showing 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. These data could be used to inform patient outcomes.