title: Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells.
abstract: Expression of the transcription factor FOXP3 characterizes regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Intra-tumoral accumulation of Tregs is associated with unfavorable prognosis in several kinds of cancers. Recently, expression of FOXP3 and its association with prognosis have also been shown in some cancer cells in clinical studies. For non-small cell lung cancer (NSCLC), however, prognostic significance of tumor FOXP3 expression and its relationship with Tregs remain unknown. FOXP3 expression in cancer cells and tumor-infiltrating lymphocytes was examined by immunohistochemical staining of surgical specimens from 87 patients with NSCLC. Prognostic values of the tumor-infiltrating Treg count and tumor FOXP3 expression status were evaluated retrospectively. FOXP3-positive cancer cells were observed in 27 of 87 (31.0%) patients. There was no significant relationship between Treg count and tumor FOXP3 status. Increased Treg counts were associated with worse overall and relapse-free survival whereas the influence of tumor FOXP3 status on survival was not significant. However, when FOXP3-positive cancer cells were present, the relationship between Treg accumulation and worse prognosis was attenuated. In contrast, patients without tumor FOXP3 expression and high Treg count had significantly worse overall and relapse-free survival (hazard ratio: 3.118 and 3.325, p=0.028 and 0.024, respectively) than other groups. These results suggest that tumor FOXP3 expression has a better prognostic potential in NSCLC and that in combination with tumor-infiltrating Treg count the absence of tumor FOXP3 allows the selection of high-risk patients.
authors: Department of Thoracic Surgery, NHO Yamaguchi-Ube Medical Center, 685 Higashi-kiwa, Ube, 755-0241, Japan. htao@yamaguchi-hosp.jp
authors: Hiroyuki
authors: H
authors: Tao
authors: Yusuke
authors: Y
authors: Mimura
authors: Keisuke
authors: K
authors: Aoe
authors: Seiki
authors: S
authors: Kobayashi
authors: Hiromasa
authors: H
authors: Yamamoto
authors: Eisuke
authors: E
authors: Matsuda
authors: Kazunori
authors: K
authors: Okabe
authors: Tsuneo
authors: T
authors: Matsumoto
authors: Kazurou
authors: K
authors: Sugi
authors: Hiroshi
authors: H
authors: Ueoka
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors