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@ARTICLE{Echterdiek:125748,
      author       = {F. Echterdiek and J. Janikovits$^*$ and L. Staffa$^*$ and
                      M. Müller$^*$ and B. Lahrmann and M. Frühschütz$^*$ and
                      B. Hartog$^*$ and N. Nelius$^*$ and A. Benner$^*$ and M.
                      Tariverdian and M. von Knebel Doeberitz$^*$ and N. Grabe and
                      M. Kloor$^*$},
      title        = {{L}ow density of {FOXP}3-positive {T} cells in normal
                      colonic mucosa is related to the presence of
                      beta2-microglobulin mutations in {L}ynch syndrome-associated
                      colorectal cancer.},
      journal      = {OncoImmunology},
      volume       = {5},
      number       = {2},
      issn         = {2162-402X},
      address      = {Austin, Tex.},
      publisher    = {Landes Bioscience},
      reportid     = {DKFZ-2017-01874},
      pages        = {e1075692 -},
      year         = {2016},
      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.},
      cin          = {G105 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)G105-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27057447},
      pmc          = {pmc:PMC4801455},
      doi          = {10.1080/2162402X.2015.1075692},
      url          = {https://inrepo02.dkfz.de/record/125748},
}