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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

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...

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Hauptverfasser: Echterdiek, Fabian Friedrich (VerfasserIn) , Janikovits, Jonas (VerfasserIn) , Staffa, Laura (VerfasserIn) , Müller, Meike (VerfasserIn) , Lahrmann, Bernd (VerfasserIn) , Frühschütz, Monika (VerfasserIn) , Hartog, Benjamin (VerfasserIn) , Nelius, Nina (VerfasserIn) , Benner, Axel (VerfasserIn) , Tariverdian, Mirjam (VerfasserIn) , Knebel Doeberitz, Magnus von (VerfasserIn) , Grabe, Niels (VerfasserIn) , Kloor, Matthias (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 26 Feb 2016
In: OncoImmunology
Year: 2016, Jahrgang: 5, Heft: 2, Pages: e1075692-1-e1075692-8
ISSN:2162-402X
DOI:10.1080/2162402X.2015.1075692
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1080/2162402X.2015.1075692
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 29.10.2024
Beschreibung:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2015.1075692

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