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

• Verfasst von: Echterdiek, Fabian Friedrich [VerfasserIn]
• Verfasst von: Janikovits, Jonas [VerfasserIn]
• Verfasst von: Staffa, Laura [VerfasserIn]
• Verfasst von: Müller, Meike [VerfasserIn]
• Verfasst von: Lahrmann, Bernd [VerfasserIn]
• Verfasst von: Frühschütz, Monika [VerfasserIn]
• Verfasst von: Hartog, Benjamin [VerfasserIn]
• Verfasst von: Nelius, Nina [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Verfasst von: Tariverdian, Mirjam [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Titel: 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
• Verf.angabe: Fabian Echterdiek, Jonas Janikovits, Laura Staffa, Meike Müller, Bernd Lahrmann, Monika Frühschütz, Benjamin Hartog, Nina Nelius, Axel Benner, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Niels Grabe, and Matthias Kloor
• E-Jahr: 2016
• Jahr: 26 Feb 2016
• Umfang: 8 S.
• Fussnoten: Gesehen am 04.05.2020
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2016
• Band/Heft Quelle: 5(2016,2) Artikel-Nummer e1075692, 8 Seiten
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2015.1075692
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Beta2-microglobulin
• Sach-SW: colorectal cancer
• Sach-SW: hereditary cancer
• Sach-SW: immunoediting
• Sach-SW: Lynch syndrome
• Sach-SW: microsatellite instability
• Sach-SW: regulatory T cells
• K10plus-PPN: 1697014259

Abstract

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.