Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation

被引:244
作者
Unitt, Esther
Marshall, Aileen
Gelson, William
Rushbrook, Simon M.
Davies, Susan
Vowler, Sarah L.
Morris, Lesley S.
Coleman, Nicholas
Alexander, Graeme J. M.
机构
[1] Univ Cambridge, Sch Clin Med, Addenbrookes NHS Trust, Dept Med, Cambridge CB2 2QQ, England
[2] Univ Cambridge, Sch Clin Med, Addenbrookes NHS Trust, Dept Histopathol, Cambridge CB2 2QQ, England
[3] Univ Forvie Site, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Ctr Appl Med Stat, Cambridge CB2 2SR, England
[4] MRC, Hutchinson Res Ctr, Canc Cell Unit, Cambridge, England
关键词
hepatocellular carcinoma (HCC); tumour-infiltrating lymphocytes (TILs); Foxp3; regulatory T cells; liver transplantation;
D O I
10.1016/j.jhep.2005.12.027
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: 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. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:246 / 253
页数:8
相关论文
共 31 条
[11]   Hepatocellular carcinoma: is current therapy really altering outcome? [J].
Johnson, PJ .
GUT, 2002, 51 (04) :459-462
[12]  
Jones Emma, 2002, Cancer Immun, V2, P1
[13]  
KAWATA A, 1992, JPN J CLIN ONCOL, V22, P256
[14]   Survival after liver transplantation for hepatocellular carcinoma [J].
Khakhar, A ;
Solano, E ;
Stell, D ;
Bloch, M ;
Dale, C ;
Burns, P ;
Ghent, C ;
Quan, D ;
McAlister, V ;
Marotta, P ;
Wall, WJ .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (07) :2438-2441
[15]   Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis [J].
Mazzaferro, V ;
Regalia, E ;
Doci, R ;
Andreola, S ;
Pulvirenti, A ;
Bozzetti, F ;
Montalto, F ;
Ammatuna, M ;
Morabito, A ;
Gennari, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (11) :693-699
[16]  
Naito Y, 1998, CANCER RES, V58, P3491
[17]   CD4(+) hepatic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular carcinoma [J].
Nakao, M ;
Sata, M ;
Saitsu, H ;
Yutani, S ;
Kawamoto, M ;
Kojiro, M ;
Itoh, K .
CELLULAR IMMUNOLOGY, 1997, 177 (02) :176-181
[18]  
Onizuka S, 1999, CANCER RES, V59, P3128
[19]   Estimating the world cancer burden: GLOBOCAN 2000 [J].
Parkin, DM ;
Bray, F ;
Ferlay, J ;
Pisani, P .
INTERNATIONAL JOURNAL OF CANCER, 2001, 94 (02) :153-156
[20]   Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: Results of a multicenter study [J].
Regimbeau, JM ;
Abdalla, EK ;
Vauthey, JN ;
Lauwers, GY ;
Durand, FO ;
Nagorney, DM ;
Ikai, I ;
Yamaoka, Y ;
Belghiti, J .
JOURNAL OF SURGICAL ONCOLOGY, 2004, 85 (01) :36-41