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


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.


CONCLUSIONS
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.
Department of Surgery, University Hospital Basel, 4031 Basel, Switzerland. uzingg@gmail.com
U
U
Zingg
M
M
Montani
D M
DM
Frey
S
S
Dirnhofer
A J
AJ
Esterman
P
P
Went
D
D
Oertli
D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012107:Research Design; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors