Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer

J Thorac Oncol. 2010 May;5(5):585-90. doi: 10.1097/JTO.0b013e3181d60fd7.


Background: Cyclooxygenase-2 (COX-2) is constitutively overexpressed in a variety of epithelial malignancies and is usually associated with a poor prognosis. COX-2-derived prostaglandin E2 transforms CD4+CD25+ T regulatory (Treg) cells (Tregs), and Tregs are thought to moderate the antitumor immune response. Herein, we investigated the prognostic value of tumor-infiltrating Treg cells and their correlation with COX-2 expression in resected non-small cell lung cancer (NSCLC).

Material and methods: Intratumoral COX-2 and Treg expression were retrospectively assessed using immunohistochemistry in paraffin-embedded samples from 100 patients who had undergone complete resections for NSCLC. The expressions of COX-2 and Foxp3, which was most specific Treg cell marker, were compared with the clinicopathological variables, and the correlation between Foxp3+ Tregs and COX-2 expression was analyzed.

Results: The recurrence-free survival (RFS) of patients with elevated COX-2 expression was significantly worse than that of patients without COX-2 expression. Tumor-infiltrating Foxp3-positive lymphocytes were positively correlated with COX-2 expression. The median count for Foxp3-positive lymphocytes was 3 (minimum-maximum, 0-24) in 10 high-power fields. The RFS of patients with tumors containing >or=3 Foxp3-positive cells (Foxp3 expression group) was significantly worse than that of patients with tumors containing <3 Foxp3-positive cells. In a multivariate analysis, only nodal status was an independent predictor of a significantly shorter RFS. However, in node-negative NSCLC, Foxp3 expression was an independent predictor of a significantly shorter RFS.

Conclusions: Tumor-infiltrating Foxp3+ Tregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS, especially among patients with node-negative NSCLC.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / surgery
  • Aged
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / surgery
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / surgery
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Neoplasm Recurrence, Local / metabolism*
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes, Regulatory / immunology*


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human