title: Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity.
abstract: Regulatory and cytotoxic T cells are key players in the host's anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions.
  
  
  
  In 202 patients 103 pre-radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of advanced rectal cancer were available and an immunohistochemical double staining of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate cell density and cell-to-cell distances.
  
  
  
  FoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged. High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival. Cell-to-cell distances of randomly distributed cells were simulated and compared to observed cell-to-cell distances. Observed distances shorter than the simulated, random distances were hypothesized to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short distances were associated with a favourable prognosis while the opposite was true for the stromal compartment.
  
  
  
  The analysis of cell-to-cell distances may offer a tool to predict outcome, maybe by identifying functionally active, interacting infiltrating inflammatory cells in different tumour compartments.
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Rebecca
authors: R
authors: Posselt
authors: Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Katharina
authors: K
authors: Erlenbach-Wünsch
authors: Department of Radiology, Charité Universitätsmedizin, Berlin, Germany.
authors: Matthias
authors: M
authors: Haas
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Jonas
authors: J
authors: Jeßberger
authors: Deparment of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Maike
authors: M
authors: Büttner-Herold
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Marlen
authors: M
authors: Haderlein
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Markus
authors: M
authors: Hecht
authors: Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Rainer
authors: R
authors: Fietkau
authors: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Luitpold V
authors: LV
authors: Distel
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D059248:Chemoradiotherapy / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: CD8+; FoxP3+; cytotoxic T cells; regulatory T cells; tumour-infiltrating lymphocytes