Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis

Xin Yuan, An Zhi Zhang, Yi Lin Ren, Xue Li Wang, Chen Hao Jiang, Lan Yang, Chun Xia Liu, Wei Hua Liang, Li Juan Pang, Wen Yi Gu, Feng Li, Jian Ming Hu, Xin Yuan, An Zhi Zhang, Yi Lin Ren, Xue Li Wang, Chen Hao Jiang, Lan Yang, Chun Xia Liu, Wei Hua Liang, Li Juan Pang, Wen Yi Gu, Feng Li, Jian Ming Hu

Abstract

Objectives: This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC).

Materials and methods: Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3.

Results: Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04).

Conclusions: It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1
Figure 1
Articles retrieved and assessed for eligibility.
Figure 2
Figure 2
A. Risk of bias summary: a review of authors’ judgments for each risk of bias item for included studies. B. Risk of bias graph: a review of authors’ judgments for each risk of bias item presented as percentages across all included studies.
Figure 3
Figure 3
Forest plot of immunophenotype assessment before and after treatment with CIK/DC-CIK. The random-effects meta-analysis model was used. CI = confidence interval, CIK/DC-CIK = immunotherapy with cytokine-induced killer cells or a combination of dendritic cells and cytokine-induced killer cells.
Figure 4
Figure 4
Forest plots of the comparisons of (A) overall survival (OS) and (B) overall response rate (ORR) and disease control rate (DCR). The fixed-effects meta-analysis model (Mantel–Haenszel method) was used. CI = confidence interval, CIK/DC-CIK = immunotherapy with cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells; cont = conventional therapy, M–H = Mantel–Haenszel method.
Figure 5
Figure 5
Forest plots of the comparisons of quality-of-life improved rate (QIR). The fixed-effects meta-analysis model (Mantel–Haenszel method) was used.
Figure 6
Figure 6
Forest plots of the comparisons of immunoglobulin levels in serum.
Figure 7
Figure 7
Forest plots of the comparisons of cytokine levels.
Figure 8
Figure 8
Forest plots of the comparisons of tumor marker levels in serum.
Figure 9
Figure 9
Forest plots of the comparisons of side effects.
Figure 10
Figure 10
Analysis of publication bias.

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Source: PubMed

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