title: Adenocarcinoma contains more immune tolerance regulatory t-cell lymphocytes (versus squamous carcinoma) in non-small-cell lung cancer.
abstract: BACKGROUND
  Regulatory T lymphocytes (Tregs) are known to have host-immune dampening effects in many tumors and to be associated with increased tumor recurrence. Pharmacologic therapies have been developed to target these cells and hence strengthen the host's immune system. The FoxP3 gene is a marker of Tregs and can be visualized with immunohistochemistry (IHC). We investigated the presence and pattern of Tregs in non-small-cell lung tumors to determine possible therapeutic targets in lung cancer.
  
  
  METHODS
  We selected archival samples of primary lung carcinoma and benign inflamed lung from 32 surgical resections. We created a tissue array containing duplicate cores from the N1 and N2 nodal stations from 16 of the cases along with paired benign lung and tumor. We used whole-slide analysis for the other 16 cases. We used FoxP3 IHC to visualize Tregs in all lymphoid tissue present and to assess the quantity and pattern within the tissues.
  
  
  RESULTS
  All lymphoid tissue contains Tregs, but adenocarcinoma had significantly higher levels than both inflammatory lung controls and squamous carcinomas (p ≤ 0.008). Benign N1 lymph nodes (from patients with lung cancer) showed higher numbers of Tregs for adenocarcinoma versus squamous carcinoma.
  
  
  CONCLUSIONS
  These findings reveal that Tregs are present in all lung tissues examined, but with significant enrichment in adenocarcinoma. This may lead to a more permissive microenvironment for adenocarcinoma and may explain aggressive patterns of tumor spread for this histology. Lung cancer patients with adenocarcinoma histology may benefit most from Treg-targeted therapy.
authors.affiliation: Department of Pathology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. Candice.C.Black@hitchcock.org
authors.forename: Candice C
authors.initials: CC
authors.lastname: Black
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Turk
authors.forename: Konstantin
authors.initials: K
authors.lastname: Dragnev
authors.forename: James R
authors.initials: JR
authors.lastname: Rigas
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D046888:Tissue Array Analysis; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors