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Echterdiek, Fabian Friedrich [Author]; Janikovits, Jonas [Author]; Staffa, Laura [Author]; Müller, Meike [Author]; Lahrmann, Bernd [Author]; Frühschütz, Monika [Author]; Hartog, Benjamin [Author]; Nelius, Nina [Author]; Benner, Axel [Author]; Tariverdian, Mirjam [Author]; Knebel Doeberitz, Magnus von [Author]; Grabe, Niels [Author]; Kloor, Matthias [Author]

Low density of FOXP3-positive T cells in normal colonic mucosa is related to the presence of beta2-microglobulin mutations in Lynch syndrome-associated colorectal cancer

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  • Media type: E-Article
  • Title: Low density of FOXP3-positive T cells in normal colonic mucosa is related to the presence of beta2-microglobulin mutations in Lynch syndrome-associated colorectal cancer
  • Contributor: Echterdiek, Fabian Friedrich [Author]; Janikovits, Jonas [Author]; Staffa, Laura [Author]; Müller, Meike [Author]; Lahrmann, Bernd [Author]; Frühschütz, Monika [Author]; Hartog, Benjamin [Author]; Nelius, Nina [Author]; Benner, Axel [Author]; Tariverdian, Mirjam [Author]; Knebel Doeberitz, Magnus von [Author]; Grabe, Niels [Author]; Kloor, Matthias [Author]
  • Published: 26 Feb 2016
  • Published in: OncoImmunology ; 5(2016), 2, Artikel-ID e1075692, Seite e1075692-1-e1075692-8
  • Language: English
  • DOI: 10.1080/2162402X.2015.1075692
  • Identifier:
  • Keywords: Beta2-microglobulin ; colorectal cancer ; hereditary cancer ; immunoediting ; Lynch syndrome ; microsatellite instability ; regulatory T cells
  • Origination:
  • Footnote:
  • Description: Microsatellite instability (MSI-H) is caused by DNA mismatch repair deficiency and occurs in 15% of colorectal cancers. MSI-H cancers generate highly immunogenic frameshift peptide (FSP) antigens, which elicit pronounced local immune responses. A subset of MSI-H colorectal cancers develops in frame of Lynch syndrome, which represents an ideal human model for studying the concept of immunoediting. Immunoediting describes how continuous anti-tumoral immune surveillance of the host eventually leads to the selection of tumor cells that escape immune cell recognition and destruction. Between 30 and 40% of Lynch syndrome-associated colorectal cancers display loss of HLA class I antigen expression as a result of Beta2-microglobulin (B2M) mutations. Whether B2M mutations result from immunoediting has been unknown. To address this question, we related B2M mutation status of Lynch syndrome-associated colorectal cancer specimens (n = 30) to CD3-positive, CD8-positive and FOXP3-positive T cell infiltration in both tumor and normal mucosa. No significant correlation between B2M mutations and immune cell infiltration was observed in tumor tissue. However, FOXP3-positive T cell infiltration was significantly lower in normal mucosa adjacent to B2M-mutant (mt) compared to B2M-wild type (wt) tumors (mean: 0.98% FOXP3-positive area/region of interest (ROI) in B2M-wt vs. 0.52% FOXP3-positive area/ROI in B2M-mt, p = 0.023). Our results suggest that in the absence of immune-suppressive regulatory T cells (Treg), the outgrowth of less immunogenic B2M-mt tumor cells is favored. This finding supports the immunoediting concept in human solid cancer development and indicates a critical role of the immune milieu in normal colonic mucosa for the course of disease.
  • Access State: Open Access