Colorectal cancer (CRC) is one of the most common cancers in New Zealand and Australia. T cells play a significant role in preventing tumour development but immunotherapies targeting these cells have been unsuccessful in CRC. This may be because tumour infilitrating T cells can be functionally and phenotypically altered by the tumour microenvironment. This study utilises flow cytometry to assess the phenotype and function of T cells from within the tumour compared to T cells from control bowel tissue in people with CRC.
There was reduced activation of the T cell infiltrate in the tumour, with fewer activated (CD69+), effector (CD69+ IFN-y+) and IL-2 producing T cells and more regulatory T cells (CD25hi FOXP3+) compared to associated control bowel tissue (n= 18-51). Surprisingly, late stage CRC tumours have a higher frequency of IL-2 producing T cells than early stage, indicating that IL-2 production could be helping cancer progression.
There is limited functional data on tumour infilatrating T cells in CRC due to the difficulty in isolating and maintaining viability of the T cells. Utilising novel methods for T cell isolation and culture we have shown that T cells from CRC tissue proliferate less than those from matched control bowel tissue (N= 5), indicating that T cells from CRC are functionally impaired. Regulatory T cells isolated from both tissue samples remain functional, however their effect can vary depending whether they are supressing target T cells isolated from tumour or bowel tissue.
Together, these data show that the T cell infiltrate in CRC tumours is phenotypically and functionally supressed. Further analysis, will elucidate why immunotherapies are failing in CRC, and discover novel ways to improve them.