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High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability.

Michel S, Benner A, Tariverdian M, Wentzensen N, Hoefler P, Pommerencke T, Grabe N, von Knebel Doeberitz M, Kloor M - Br. J. Cancer (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Partnership Unit (MMPU), Department of Applied Tumour Biology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg 69120, Germany.

ABSTRACT
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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Representative immunohistochemical stainings with antibodies specific for FOXP3 (upper panel), CD3 (lower left panel) and CD8 (lower right panel). Detailed view of FOXP3 staining (upper right) shows the presence of FOXP3-positive cells infiltrating the tumour epithelium (arrow).
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fig1: Representative immunohistochemical stainings with antibodies specific for FOXP3 (upper panel), CD3 (lower left panel) and CD8 (lower right panel). Detailed view of FOXP3 staining (upper right) shows the presence of FOXP3-positive cells infiltrating the tumour epithelium (arrow).

Mentions: Infiltration of the tumour with FOXP3-positive cells was observed in all CRC specimens. In all tumours, the number of infiltrating FOXP3-positive cells was higher in the tumour stroma than in the epithelium. In addition to the staining for FOXP3, all tumours were stained with antibodies against CD3 and CD8 to assess the overall infiltration with CD3-positive T cells and with CD8-positive T cells. As observed for the FOXP3 stain, all tumours showed infiltration with CD3-positive and CD8-positive lymphocytes, which was higher in the tumour stroma than in the epithelium. The median values for the intraepithelial and stromal infiltration of MSI-H and MSS CRCs with FOXP3-positive, CD3-positive and CD8-positive lymphocytes are summarised in Table 2. The exemplary staining results are displayed in Figure 1.


High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability.

Michel S, Benner A, Tariverdian M, Wentzensen N, Hoefler P, Pommerencke T, Grabe N, von Knebel Doeberitz M, Kloor M - Br. J. Cancer (2008)

Representative immunohistochemical stainings with antibodies specific for FOXP3 (upper panel), CD3 (lower left panel) and CD8 (lower right panel). Detailed view of FOXP3 staining (upper right) shows the presence of FOXP3-positive cells infiltrating the tumour epithelium (arrow).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600708&req=5

fig1: Representative immunohistochemical stainings with antibodies specific for FOXP3 (upper panel), CD3 (lower left panel) and CD8 (lower right panel). Detailed view of FOXP3 staining (upper right) shows the presence of FOXP3-positive cells infiltrating the tumour epithelium (arrow).
Mentions: Infiltration of the tumour with FOXP3-positive cells was observed in all CRC specimens. In all tumours, the number of infiltrating FOXP3-positive cells was higher in the tumour stroma than in the epithelium. In addition to the staining for FOXP3, all tumours were stained with antibodies against CD3 and CD8 to assess the overall infiltration with CD3-positive T cells and with CD8-positive T cells. As observed for the FOXP3 stain, all tumours showed infiltration with CD3-positive and CD8-positive lymphocytes, which was higher in the tumour stroma than in the epithelium. The median values for the intraepithelial and stromal infiltration of MSI-H and MSS CRCs with FOXP3-positive, CD3-positive and CD8-positive lymphocytes are summarised in Table 2. The exemplary staining results are displayed in Figure 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Partnership Unit (MMPU), Department of Applied Tumour Biology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg 69120, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus