Tumour-infiltrating lymphocytes and survival in patients with adenocarcinoma of the oesophagus

Eur J Surg Oncol. 2010 Jul;36(7):670-7. doi: 10.1016/j.ejso.2010.05.012. Epub 2010 May 26.


Introduction: Tumor-infiltrating lymphocytes (TILs) and forkhead box transcription factor positive (FoxP3(+)) regulatory T-lymphocytes (TREGs) have been analyzed in a variety of tumors but not in oesophageal adenocarcinoma.

Patients and methods: Tissue from 130 adenocarcinomas of the oesophagus was re-evaluated in the centre and periphery of tumour, respectively, using immunohistochemical staining with anti-CD3, anti-CD4, anti-CD8, anti-CD25 and anti-FoxP3 antibodies. Patients were stratified according neoadjuvant treatment. 106 patients proceeded directly to surgery and 24 underwent pre-operative radio-chemotherapy (RCT).

Results: In patients without RCT, TILs were found significantly more frequently in the periphery with the exception of CD25(+) cells. Patients with centrally low counts of FoxP3(+) TREGs had higher tumour stages than patients with high counts (p < 0.011). The number of FoxP3(+) TREGs was significantly associated with the number of CD8(+) cells (centre: p < 0.001, periphery: p = 0.002). The multivariate regression analysis identified UICC stage (IIB/III vs. I/IIA, hazard ratio 2.6, p = 0.011) and completeness of resection (no vs. yes, hazard ratio 2.3, p = 0.015) as independent predictors of survival. RCT significantly reduced the number of TREGs in the centre (p = 0.016) but not the number of the other TILs.

Conclusion: UICC stage and completeness of resection but none of the TILs were prognostic markers for long-term survival. We found no morphologic evidence that TREGs suppress immunological response, represented by the infiltration of CD8(+) cells. Preoperative RCT affected the centre of tumours more than the periphery, which may indicate that it does not inhibit the host-to-tumour reaction. RCT affects TREGs more than the other TILs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Chemotherapy, Adjuvant
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / therapy
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Research Design
  • Survival Analysis
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*


  • FOXP3 protein, human
  • Forkhead Transcription Factors