Journal
BRITISH JOURNAL OF CANCER
Volume 99, Issue 11, Pages 1867-1873Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6604756
Keywords
colorectal cancer; microsatellite instability; regulatory T cells; tumour immunity; immune evasion
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Funding
- Deutsche Krebshilfe (German Cancer Aid)
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High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorectal cancers has not been analysed yet. Using an antibody directed against the regulatory T-cell marker transcription factor forkhead box P3 (FOXP3), regulatory T cells were examined in 70 colorectal cancers with known MSI status (MSI-H, n = 37; microsatellite stable, n = 33). In MSI-H colorectal cancers, we found a significantly higher intraepithelial infiltration with FOXP3-positive cells (median: 8.5 cells per 0.25 mm(2) vs 3.1 cells per 0.25 mm(2) in microsatellite stable, P < 0.001), and a significantly elevated ratio of intraepithelial to stromal infiltration (0.05 vs 0.01 in microsatellite stable, P < 0.001). CD8-positive cell counts were related positively to the number of FOXP3-positive cells (Spearman's rho = 0.56 and 0.55, respectively). Our results show that the elevated number of CD8-positive lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8-negative FOXP3-positive cells. These data suggest that FOXP3-positive cells may play a role in the regulation of the immune response directed against MSI-H colorectal cancers at the primary tumour site.
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