Density of tumor-infiltrating FOXP3+ T cells as a response marker for induction chemoradiotherapy and a potential prognostic factor in patients treated with trimodality therapy for locally advanced non-small cell lung cancer

Ann Thorac Cardiovasc Surg. 2014;20(6):980-6. doi: 10.5761/atcs.oa.13-00237. Epub 2014 Feb 28.

Abstract

Purpose: To examine the relationship between the density of tumor-infiltrating T cell subpopulations and the pathological response to induction chemoradiotherapy (CRT) in patients with locally advanced NSCLC, and to assess the impact of T cell density on patient prognosis.

Methods: A total of 64 patients with c-stages IIA-IIIB NSCLC who underwent induction CRT followed by R0 surgery were enrolled. Tumor-infiltrating T cells expressing either FOXP3 or CD8 were detected by immunohistochemical staining.

Results: Mean numbers of tumor-infiltrating FOXP3+ T cells were 39.9 for patients with minor pathological responses (n = 9), 18.4 for those with major pathological responses (n = 25), and 12.9 for those with complete pathological responses (n = 30; P <0.001). The number of CD8+ T cells was not associated with pathological responses. Patients with lower FOXP3+ T cell densities showed better survival, although the difference was not statistically significant.

Conclusion: Our study demonstrated that the density of tumor-infiltrating FOXP3+ T cells indicated the degree of response for induction CRT and prognosis in patients treated with trimodality therapy for locally advanced NSCLC, suggesting that FOXP3+ T cells may be target for adjunct immunotherapy.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chemoradiotherapy, Adjuvant* / mortality
  • Chemotherapy, Adjuvant
  • Female
  • Forkhead Transcription Factors / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Neoplasm Staging
  • Pneumonectomy* / adverse effects
  • Pneumonectomy* / mortality
  • Predictive Value of Tests
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors