Adaptive immunity in microscopic colitis and colon cancer

Chronic inflammation is a common cause of cancer, but activation of the immune system has also been shown to eliminate dysplastic cells and suppress cancer. Whereas Ulcerative colitis (UC) is associated with increased risk of colitis associated colon cancer, Microscopic colitis (MC), a common cause of chronic diarrhea in developed countries with hitherto unknown etiology, is associated with reduced risk of colorectal cancer, compared with UC, but also the general population. Thus, under certain conditions chronic activation of the mucosal immune system can protect from colonic dysplasia. In contrast to UC, being dominated by CD4+ T cells, in MC an augmented number of CD8+ T lymphocytes, a cell type associated with immune surveillance and immune defense against tumor cells, is seen as well. However, the role of CD8+ T cells in chronic intestinal inflammations is not well studied. The goal is to enhance the understanding of the role of CD8+ T cells in protection against colon cancer in MC patients and in development of MC, through careful characterization of these cells. UC patients and non-inflamed controls are investigated for comparison. Our hypothesis is that CD8+ T lymphocytes, in addition to mediating the colonic inflammation in MC, contribute to immune surveillance against tumors, possibly explaining the reduced risk of colon cancer in MC patients. Enhanced knowledge of the function of CD8+ T lymphocytes in MC will help in understanding why MC patients have a lower risk of colorectal cancer, and the role of CD8+ T cells in immune surveillance in the colonic mucosa. This can contribute to new therapeutic strategies for MC and other inflammatory conditions associated with enhanced cancer risk, e.g. by inhibiting or stimulating specific molecules in the immune response.

Research projects

• The impact of a proprietary semi-automated workflow on gene expression analysis: implications for biological interpretation
• Cytokines and CD8 ⁺ CTL-associated cytotoxic proteins in colonic biopsies
• Flow cytometric analysis of jejunal mucosal lymphocytes in microscopic colitis
• Next generation sequencing (NGS)-based gene expression analysis of genes involved in tumor transformation and immune surveillance in colonic biopsies from microscopic colitis patients
• Next generation sequencing (NGS)-based gene expression analysis of genes involved in tumor transformation and immune surveillance in colonic tissue from G-alpha-i2-deficient mice with or without colitis and colon cancer
• An in vitro model to evaluate the impact of soluble factors from the colonic mucosa of microscopic colitis patients on CD8+ T lymphocytes
• The connection between T lymphocyte subtype surface expression of immune markers and functional phenotype in acute covid-19 infection and its impact on clinical prognosis