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

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.