Autologous transplantation of cytokine-induced killer cells as an adjuvant therapy for hepatocellular carcinoma in Asia: an update meta-analysis and systematic review

Abstract

BackgroundHigh recurrence rate after curative treatment is the major problem for hepatocellular carcinoma (HCC). Cytokine-induced killer cells (CIKs) therapy was extensively studied among HCC patients. However, the value of CIKs therapy was controversial. A meta-analysis was performed to investigate the efficacy of adjuvant CIKs after invasive treatments among HCC patients.MethodsWe searched online for literatures studying sequential CIKs therapy for HCC patients. Recurrence-free survival (RFS), progress-free survival (PFS) and overall survival (OS) were set as the main endpoints. Both overall and subgroup analysis were accomplished.ResultsA total of 12 clinical trials with 1,387 patients were included. The pooled analysis showed a significant improvement of RFS, PFS and OS in CIK group (HR 0.56, 95% CI 0.47-0.67, p<0.00001 for RFS; HR 0.53, 95% CI 0.40-0.69, p<0.00001 for PFS; HR 0.59, 95% CI 0.46-0.77, p<0.0001 for OS). The proportion of CD4+ T cells increased significantly, while CD8+ T cells decreased significantly after CIKs therapy (WMD 4.07, 95% CI 2.58-5.56, p<0.00001; WMD -2.84, 95% CI -4.67 to -1.01, p=0.002, respectively). No significant differences of adverse events between CIK and non-CIK group existed.ConclusionsConventionally invasive therapies combined with CIKs therapy could improve the prognosis of HCC patients, especially for RFS and PFS, with mild side effects. Optimizing patient selection shall be the direction in future studies.

Immunotherapy for hepatocellular carcinoma: Current and future

“…This showed an improvement of 14 mo in recurrence free survival[83]. A systematic review and meta-analysis of CIK cell therapy in HCC in Asia reached similar conclusions that in selected patients, progression free survival and recurrence free survival are improved[84].…”

Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up

“…Recently, another RCT also showed that CIK cell treatment significantly increased time-to-recurrence after curative resection [ 34 ]. A recent meta-analysis involving 12 RCTs evaluating the efficacy of adjuvant autologous CIK cell treatment showed that CIK cell treatment significantly prolonged both RFS (pooled HR 0.56; 95% CI 0.47–0.67) and OS (HR 0.59; 95% CI 0.46–0.77) although heterogeneity was moderate (both I 2 = 48%) [ 35 ]. Among eight RCTs that evaluated RFS as an endpoint, seven trials demonstrated that CIK cell treatment significantly improved RFS with HRs ranging from 0.14 to 0.63 [ 2 , 15 – 17 , 36 , 37 ].…”

Clinical applications of dendritic cells&ndash;cytokine-induced killer cells mediated immunotherapy for pancreatic cancer: an up-to-date meta-analysis

“…Sensitivity analysis was conducted to evaluate the consistency of the results and evaluate the influence of single studies on overall risk estimate. 23 …”