title: Influence of neoadjuvant radio-chemotherapy on tumor-infiltrating lymphocytes in squamous esophageal cancer.
abstract: BACKGROUND
  Data on influence of radio-chemotherapy (RCT) on tumor-infiltrating lymphocytes (TILs) is scarce and no study addressed this issue in esophageal squamous cell cancer (SCC) so far.
  
  
  METHODS
  Tumor specimens of 49 patients with SCC were re-evaluated with immunohistochemical staining with anti-CD3, anti-CD4, anti-CD8, anti-CD25 and anti-FOXP3 antibodies. Lymphocytes were counted in one high power field (0.189 mm(2)) at the periphery and in the centre of tumors.
  
  
  RESULTS
  21 patients received preoperative RCT, 28 proceeded directly to surgery. There was no significant difference in survival between the two groups (median survival 23.2 months vs. 22.1 months, log rank test p=n.s.). Cox regression analysis showed that no variable had a significant effect on survival. The infiltrating pattern of TILs revealed higher numbers peripherally independent of the administration of RCT. There was a significant decrease in all cell numbers except CD4(+) cells in the centre of the tumors after RCT (CD3(+)p=0.005; CD8(+)p=0.02; CD25(+)p=0.01; FoxP3(+)p=0.01). There were fewer TILs in the periphery after RCT; however, this difference only reached significance in FoxP3(+) cells (p=0.01).
  
  
  CONCLUSIONS
  Neoadjuvant RCT reduced the number of TILs in esophageal SCC. This was primarily seen in the centre of tumors and suggests that the effect of RCT on immunological response is located in the centre of tumors.
authors.affiliation: Department of Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland. uzingg@uhbs.ch
authors.forename: U
authors.initials: U
authors.lastname: Zingg
authors.forename: M
authors.initials: M
authors.lastname: Montani
authors.forename: D M
authors.initials: DM
authors.lastname: Frey
authors.forename: S
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: P
authors.initials: P
authors.lastname: Went
authors.forename: D
authors.initials: D
authors.lastname: Oertli
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy*; D016009:Chi-Square Distribution; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome