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@ARTICLE{Miyan:130180,
      author       = {M. Miyan and J. Schmidt-Mende and R. Kiessling and I.
                      Poschke$^*$ and J. de Boniface},
      title        = {{D}ifferential tumor infiltration by {T}-cells
                      characterizes intrinsic molecular subtypes in breast
                      cancer.},
      journal      = {Journal of translational medicine},
      volume       = {14},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2017-05260},
      pages        = {227},
      year         = {2016},
      abstract     = {Molecular subtypes of breast cancer and presence of
                      tumor-infiltrating immune cells have both been implicated as
                      important predictive and prognostic factors for improved
                      risk stratification and treatment individualization of
                      breast cancer patients. Their association, however, has not
                      been studied in detail. The aim of this study was to
                      evaluate the expression of the T cell markers CD8, FoxP3,
                      CD3 and ζ-chain in molecular subtypes of the invasive
                      margin and tumor center of breast cancer and corresponding
                      sentinel nodes and to deduct prognostic information from
                      these findings.Tumor and sentinel node sections from 177
                      patients with primary, invasive, unilateral early-stage
                      breast cancer were stained by immunohistochemistry and
                      T-cell phenotypes quantified manually. Clinical data were
                      collected from medical records.The degree of T-cell
                      infiltration and expression of all markers differed
                      significantly among the molecular subtypes, being highest in
                      non-luminal, more aggressive tumors: more T-cell
                      infiltration and higher expression of all markers were
                      associated with hormone receptor negativity, higher
                      proliferation and higher histological grades, but also with
                      larger tumor size. Basal-like tumors, and most remarkably
                      their tumor centers, hosted the highest number of
                      FoxP3+ T-cells with an unfavorable ratio to cytotoxic
                      CD8+ T-cells. T-cell infiltration was generally higher in
                      the invasive margin than the tumor center. A scoring system
                      based on densities of CD3 and CD8 could significantly
                      separate molecular subtypes (p < 0.001).Thus,
                      immunological patterns with functional implications within
                      each subtype are associated with prognostic factors. These
                      findings should be further validated in studies using larger
                      patient populations and longer follow-up.},
      keywords     = {Antigens, CD (NLM Chemicals) / Biomarkers (NLM Chemicals)},
      cin          = {G180},
      ddc          = {610},
      cid          = {I:(DE-He78)G180-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27473163},
      pmc          = {pmc:PMC4966793},
      doi          = {10.1186/s12967-016-0983-9},
      url          = {https://inrepo02.dkfz.de/record/130180},
}