Inflammatory and regulatory T cells contribute to a unique immune microenvironment in tumor tissue of colorectal cancer patients (P2145)

Abstract

Abstract Colorectal cancer (CRC) is a leading causes of cancer mortality. T cells play a crucial role in the elimination of cancer. Despite their importance little in known about the composition of the T cell subsets in CRC and how the cancer cells can affect these subsets. Using a novel analytical flow cytometric approach, we have analysed T cell subsets in CRC tumor tissue and matched non-transformed bowel tissue. We discovered that the tumor has a lower frequency of effector T cells, but a higher frequency of both regulatory and inflammatory T cells, compared with associated non-transformed bowel tissue. To study the functional interactions of these cell subsets, methods have been established to isolate live, unmanipulated T cell subsets from tumor tissue and non-transformed bowel tissue. Effector T cells (IFNγ +), regulatory T cells (CD25hi, FoxP3+) and inflammatory T cells (IL-17+) have been isolated from CRC tumor tissue or non-transformed bowel tissue. Ex vivo studies have shown that effector T cells from the tumor tissue proliferate less, and are unable to produce IL-2 upon stimulation, than effector T cells from non-transformed bowel tissue. In addition, regulatory T cells isolated from non-transformed bowel tissue actively inhibit proliferation of T cells from the same tissue. These data describe an immune microenvironment in colorectal cancer unique, in both phenotype and function, to the tumor tissue and distinct from the surrounding non-transformed bowel tissue.