Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation.
OBJECTIVE
Liver transplantation is an effective treatment for highly selected patients with hepatocellular carcinoma (HCC), but tumour recurrence remains an important cause of mortality. There are few data on the relation between the recurrence of HCC and lymphocytic infiltration following liver transplantation.


METHODS
The tumour CD4+, CD8+, CD25+ and Foxp3+ lymphocyte infiltrate was assessed by immunohistochemistry in explant tissue of 69 patients who underwent liver transplantation for HCC between 1985 and 2001. The data were analysed according to HCC recurrence and factors known to be associated with outcome.


RESULTS
Tumour size (Hazard ratio (95% CI: 1.19 (1.02, 1.39), P = 0.03)), vascular invasion (P = 0.02), lymphocyte infiltration (P = 0.02) and CD4:CD8 ratio (P = 0.001) were identified as significant univariate predictors of tumour recurrence. On multivariate analysis CD4:8 ratio (P = 0.001), vascular invasion (P = 0.01), tumour size (P = 0.06) and reduced lymphocyte infiltration (P = 0.03) were significant independent predictors of recurrence. The presence of Foxp3+ T-lymphocytes was not predictive of recurrence, but was associated with vascular invasion (FE = 9.02, P = 0.04).


CONCLUSIONS
The data support the hypothesis that immune responses are important in HCC and that the phenotype of infiltrating lymphocytes is informative regarding prognosis.
Unitt
Esther
E
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's NHS Trust, Hills Road, Cambridge CB2 2QQ, UK.
Marshall
Aileen
A
Gelson
William
W
Rushbrook
Simon M
SM
Davies
Susan
S
Vowler
Sarah L
SL
Morris
Lesley S
LS
Coleman
Nicholas
N
Alexander
Graeme J M
GJ
D016516:CD4-CD8 Ratio; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit