Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 10/2011

01-10-2011 | Original Paper

An immune function assay predicts post-transplant recurrence in patients with hepatocellular carcinoma

Authors: Jian-Wen Cheng, Ying-Hong Shi, Jia Fan, Xiao-Wu Huang, Shuang-Jian Qiu, Yong-Sheng Xiao, Zheng Wang, Zhi Dai, Zhao-You Tang, Jian Zhou

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2011

Login to get access

Abstract

Purpose

An immune function assay has been proposed as a new strategy to monitor immunosuppression after organ transplantation. However, there are limited data regarding its role in liver transplant recipients with hepatocellular carcinoma (HCC). In this study, we sought to determine the utility of this functional assay in assessing the risk of infection, rejection, and tumor recurrence in liver transplant recipients.

Methods

Immune function was determined by ImmuKnow assay that measures the amount of adenosine triphosphate (ATP) produced by CD4 (+) T cells to monitor the global immune status in 342 whole blood samples from 105 liver transplant recipients. The association between ATP value and post-transplant tumor recurrence was evaluated in 60 HCC patients. The ATP value in predicting tumor recurrence in other independent cohort of 92 recipients with HCC was analyzed prospectively.

Results

The mean ATP values of liver transplant recipients with infection (145.2 ± 87.0 ng/ml) or acute rejection (418.9 ± 169.5 ng/ml) were different from those with stable state (286.6 ± 143.9 ng/ml, P < 0.05). In recipients with HCC who developed recurrent tumors, the values were significantly lower than those without recurrence (137.8 ± 66.4 vs. 289 ± 133.9 ng/ml, P < 0.01); the optimal threshold value to predict post-transplant tumor recurrence was 175 ng/ml. Comparing with the patients in lower immune group (ATP ≤ 175 ng/ml), patients in the higher immune group (ATP > 175 ng/ml) experienced significantly better disease-free survival (P < 0.01). Multivariate Cox regression analysis showed the ATP value was an independent predictor of HCC recurrence.

Conclusions

The immune function assay has the potential to assess the risk of infection and rejection in liver transplantation and to predict post-transplant tumor recurrence in recipients with HCC.
Appendix
Available only for authorised users
Literature
go back to reference Dirks NL, Huth B, Yates CR, Meibohm B (2004) Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther 42(12):701–718PubMed Dirks NL, Huth B, Yates CR, Meibohm B (2004) Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther 42(12):701–718PubMed
go back to reference Gray JW (2003) Evidence emerges for early metastasis and parallel evolution of primary and metastatic tumors. Cancer Cell 4(1):4–6PubMedCrossRef Gray JW (2003) Evidence emerges for early metastasis and parallel evolution of primary and metastatic tumors. Cancer Cell 4(1):4–6PubMedCrossRef
go back to reference Hashimoto K, Miller C, Hirose K, Diago T, Aucejo F, Quintini C, Eghtesad B, Corey R, Yerian L, Lopez R, Zein N, Fung J (2009) Measurement of CD4+ T-cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation. Clin Transplant. doi:10.1111/j.1399-0012.2009.01169.x Hashimoto K, Miller C, Hirose K, Diago T, Aucejo F, Quintini C, Eghtesad B, Corey R, Yerian L, Lopez R, Zein N, Fung J (2009) Measurement of CD4+ T-cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation. Clin Transplant. doi:10.​1111/​j.​1399-0012.​2009.​01169.​x
go back to reference Husain S, Raza K, Pilewski JM, Zaldonis D, Crespo M, Toyoda Y, Shutt K, Spichty K, Bentlejewski C, Pakstis DL, Carey ME, McCurry KR, Zeevi A (2009) Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation 87(12):1852–1857. doi:10.1097/TP.0b013e3181a75ad2 PubMedCrossRef Husain S, Raza K, Pilewski JM, Zaldonis D, Crespo M, Toyoda Y, Shutt K, Spichty K, Bentlejewski C, Pakstis DL, Carey ME, McCurry KR, Zeevi A (2009) Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation 87(12):1852–1857. doi:10.​1097/​TP.​0b013e3181a75ad2​ PubMedCrossRef
go back to reference Kowalski R, Post D, Schneider MC, Britz J, Thomas J, Deierhoi M, Lobashevsky A, Redfield R, Schweitzer E, Heredia A, Reardon E, Davis C, Bentlejewski C, Fung J, Shapiro R, Zeevi A (2003) Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant 17(2):77–88PubMedCrossRef Kowalski R, Post D, Schneider MC, Britz J, Thomas J, Deierhoi M, Lobashevsky A, Redfield R, Schweitzer E, Heredia A, Reardon E, Davis C, Bentlejewski C, Fung J, Shapiro R, Zeevi A (2003) Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant 17(2):77–88PubMedCrossRef
go back to reference Kowalski RJ, Post DR, Mannon RB, Sebastian A, Wright HI, Sigle G, Burdick J, Elmagd KA, Zeevi A, Lopez-Cepero M, Daller JA, Gritsch HA, Reed EF, Jonsson J, Hawkins D, Britz JA (2006) Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation 82(5):663–668. doi:10.1097/01.tp.0000234837.02126.70 PubMedCrossRef Kowalski RJ, Post DR, Mannon RB, Sebastian A, Wright HI, Sigle G, Burdick J, Elmagd KA, Zeevi A, Lopez-Cepero M, Daller JA, Gritsch HA, Reed EF, Jonsson J, Hawkins D, Britz JA (2006) Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation 82(5):663–668. doi:10.​1097/​01.​tp.​0000234837.​02126.​70 PubMedCrossRef
go back to reference Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699PubMedCrossRef Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699PubMedCrossRef
go back to reference Mueller XM (2004) Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 77(1):354–362PubMedCrossRef Mueller XM (2004) Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 77(1):354–362PubMedCrossRef
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108PubMedCrossRef
go back to reference Rossano JW, Denfield SW, Kim JJ, Price JF, Jefferies JL, Decker JA, Smith EO, Clunie SK, Towbin JA, Dreyer WJ (2009) Assessment of the Cylex ImmuKnow cell function assay in pediatric heart transplant patients. J Heart Lung Transplant 28(1):26–31. doi:10.1016/j.healun.2008.10.001 PubMedCrossRef Rossano JW, Denfield SW, Kim JJ, Price JF, Jefferies JL, Decker JA, Smith EO, Clunie SK, Towbin JA, Dreyer WJ (2009) Assessment of the Cylex ImmuKnow cell function assay in pediatric heart transplant patients. J Heart Lung Transplant 28(1):26–31. doi:10.​1016/​j.​healun.​2008.​10.​001 PubMedCrossRef
go back to reference Rovira P, Mascarell L, Truffa-Bachi P (2000) The impact of immunosuppressive drugs on the analysis of T cell activation. Curr Med Chem 7(7):673–692PubMed Rovira P, Mascarell L, Truffa-Bachi P (2000) The impact of immunosuppressive drugs on the analysis of T cell activation. Curr Med Chem 7(7):673–692PubMed
go back to reference Serban G, Whittaker V, Fan J, Liu Z, Manga K, Khan M, Kontogianni K, Padmanabhan A, Cohen D, Suciu-Foca N, Ratner L, Colovai AI (2009) Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy. Hum Immunol 70(11):882–890. doi:10.1016/j.humimm.2009.07.027 PubMedCrossRef Serban G, Whittaker V, Fan J, Liu Z, Manga K, Khan M, Kontogianni K, Padmanabhan A, Cohen D, Suciu-Foca N, Ratner L, Colovai AI (2009) Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy. Hum Immunol 70(11):882–890. doi:10.​1016/​j.​humimm.​2009.​07.​027 PubMedCrossRef
go back to reference Venkataramanan R, Shaw LM, Sarkozi L, Mullins R, Pirsch J, MacFarlane G, Scheller D, Ersfeld D, Frick M, Fitzsimmons WE, Virji M, Jain A, Brayman KL, Shaked A (2001) Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 41(5):542–551PubMedCrossRef Venkataramanan R, Shaw LM, Sarkozi L, Mullins R, Pirsch J, MacFarlane G, Scheller D, Ersfeld D, Frick M, Fitzsimmons WE, Virji M, Jain A, Brayman KL, Shaked A (2001) Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 41(5):542–551PubMedCrossRef
go back to reference Vivarelli M, Cucchetti A, Piscaglia F, La Barba G, Bolondi L, Cavallari A, Pinna AD (2005) Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression. Liver Transpl 11(5):497–503. doi:10.1002/lt.20391 PubMedCrossRef Vivarelli M, Cucchetti A, Piscaglia F, La Barba G, Bolondi L, Cavallari A, Pinna AD (2005) Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression. Liver Transpl 11(5):497–503. doi:10.​1002/​lt.​20391 PubMedCrossRef
go back to reference Vivarelli M, Cucchetti A, La Barba G, Ravaioli M, Del Gaudio M, Lauro A, Grazi GL, Pinna AD (2008) Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence. Ann Surg 248(5):857–862. doi:10.1097/SLA.0b013e3181896278 PubMedCrossRef Vivarelli M, Cucchetti A, La Barba G, Ravaioli M, Del Gaudio M, Lauro A, Grazi GL, Pinna AD (2008) Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence. Ann Surg 248(5):857–862. doi:10.​1097/​SLA.​0b013e3181896278​ PubMedCrossRef
go back to reference Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9(4):416–423. doi:10.1038/nm843 PubMedCrossRef Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9(4):416–423. doi:10.​1038/​nm843 PubMedCrossRef
go back to reference Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, Busuttil RW (2008) Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg 143(2):182–188. doi:10.1001/archsurg.2007.39 (discussion 188)PubMedCrossRef Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, Busuttil RW (2008) Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg 143(2):182–188. doi:10.​1001/​archsurg.​2007.​39 (discussion 188)PubMedCrossRef
Metadata
Title
An immune function assay predicts post-transplant recurrence in patients with hepatocellular carcinoma
Authors
Jian-Wen Cheng
Ying-Hong Shi
Jia Fan
Xiao-Wu Huang
Shuang-Jian Qiu
Yong-Sheng Xiao
Zheng Wang
Zhi Dai
Zhao-You Tang
Jian Zhou
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 10/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1014-0

Other articles of this Issue 10/2011

Journal of Cancer Research and Clinical Oncology 10/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine