Research Papers:

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

Xiu-Rong Cai, Xing Li, Jin-Xiang Lin, Tian-Tian Wang, Min Dong, Zhan-Hong Chen, Chang-Chang Jia, Ying-Fen Hong, Qu Lin and Xiang-Yuan Wu _

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Oncotarget. 2017; 8:31318-31328. https://doi.org/10.18632/oncotarget.15454

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Xiu-Rong Cai1,2,*, Xing Li1,2,*, Jin-Xiang Lin1, Tian-Tian Wang1,2, Min Dong1,2, Zhan-Hong Chen1,2, Chang-Chang Jia2,3, Ying-Fen Hong1,2, Qu Lin1,2 and Xiang-Yuan Wu1,2

1Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China

2Guangdong provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, People’s Republic of China

3Cell-gene Therapy Translational Medicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Xiang-Yuan Wu, email: [email protected]

Qu Lin, email: [email protected]

Keywords: cytokine induced killer cell, liver cancer, adoptive cells therapy, immunotherapy, meta-analysis

Received: June 13, 2016    Accepted: November 12, 2016    Published: February 17, 2017


Background: High 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.

Methods: We 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.

Results: A 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.

Conclusions: Conventionally 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.

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