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

Figures & data

Figure 1 Flow diagram of the selection process.

Table 1 Clinical information from the eligible trials used in the meta-analysis

Authors	Year	Stage	Exp regimens	Patients, Con/Exp groups	Age, years		Culture conditions	Cell dose (cycles)
					Con	Exp
Chang et al^Citation28	2013	III–IV	CT, CIK	33/33	66 (median)	66 (median)	IFN-γ, IL-2, OKT-3	1×10^9/cycle (2 cycles)
Hu^Citation29	2012	III–IV	CM, CT, CIK	25/37	ND	ND	IFN-γ, IL-1, IL-2	>1×10^9/cycle (ND)
Liu et al^Citation30	2011	III–IV	CT, CIK	20/20	62 (median)	62 (median)	IFN-γ, IL-2, OKT-3	(0.6–1.6)×10^10/cycle (3 cycles)
Qu et al^Citation31	2015	IV	CT, CIK	100/100	56.3±7.5 (mean)	56.3±7.5 (mean)	IFN-γ, OKT-3, IL-2, IL-12	ND (ND)
Shu et al^Citation32	2015	II–III	RT, CT, CIK	30/30	59 (median)	57 (median)	IFN-γ, OKT-3, IL-2	5×10^10/cycle (ND)
Wang et al^Citation33,Citation41	2014	I–IV	CT, DC-CIKa	62/62	ND	ND	IFN-γ, IL-2, OKT-3 (CIK) GM-CSF, IL-4, IFN-γ (DC)	2×10^10/cycle (ND)
Xi et al^Citation34	2015	II–IIIB	Surgery, CT, DC-CIKa	26/26	62 (median)	60 (median)	IFN-γ, IL-1, IL-2, OKT-3 (CIK) GM-CSF, IL-4, TNF-α, IL-1 (DC)	3–4×10^9/cycle (2 cycles)
Xu et al^Citation35	2010	III–IV	CT, CIK	25/21	42 (mean)	45 (mean)	IFN-γ, IL-1α, IL-2, OKT-3	.5×10^9/cycle (4 cycles)
Yan et al^Citation26	2015	I–IV	RT, DC-CIKb	34/34	71.6±2.2 (mean)	70.5±2.9 (mean)	IFN-γ, IL-1α, IL-2, OKT-3 (CIK) GM-CSF, IL-4 (DC)	5×10^9/cycle (CIK) 5×10^7/cycle (DC) (ND)
Yang et al^Citation36	2015	ND	CT, DC-CIKa	100/100	72.3±6.9 (mean)	70.2±7.3 (mean)	ND	ND (1–2 cycles)
Zhu and Zhang^Citation37	2014	ND	CT, CIK	38/38	59.8±1.4 (mean)	59.6±1.3 (mean)	ND	ND (ND)

Notes: The table summarizes patients’ basic information regarding the tumor stage, treatment regimens, cases, age and details of the immunotherapy (culture conditions, cell doses and the treatment courses).

a DCs cultivated with CIK before injection;

b coinjection of DCs with CIKs.

Abbreviations: CD, cluster of differentiation; CIK, cytokine-induced killer cell; CM, Chinese medicine (Huisheng oral liquid); Con, control group; CT, chemotherapy; DC, dendritic cell; Exp, experimental group; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; OKT-3, CD3 monoclonal antibodies; ND, not determined; RT, radiotherapy; TNF, tumor necrosis factor.

Figure 2 Review of authors’ judgments about each risk of bias item for included studies.

Notes: (A) Risk of bias summary. (B) Risk of bias graph: review of authors’ judgments about each risk of bias item presented as percentages across all included studies.

Figure 3 Forest plots of the comparisons of (A) OS and (B) ORR and DCR.

Note: The fixed-effects meta-analysis model (Mantel–Haenszel method) was used.
Abbreviations: 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; DCR, disease control rate; M–H, Mantel–Haenszel method; ORR, overall response rate; OS, overall survival.

Figure 4 Forest plot for the comparison of QIR.

Note: The fixed-effects meta-analysis model (Mantel–Haenszel method) was used.
Abbreviations: 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; QIR, quality-of-life improved rate.

Figure 5 Forest plot of immunophenotype assessment before and after treatment with CIK/DC-CIK.

Note: The random-effects meta-analysis model (Mantel–Haenszel method) was used in this analysis.
Abbreviations: CD, cluster of differentiation; CI, confidence interval; CIK/DC-CIK, immunotherapy with cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells; SD, standard deviation.

Figure 6 Forest plot of cytokines before and after treatment with CIK/DC-CIK.

Note: The fixed-effects meta-analysis model (Mantel–Haenszel method) was used in this analysis.
Abbreviations: CI, confidence interval; CIK/DC-CIK, immunotherapy with cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells; IFN, interferon; IL, interleukin; SD, standard deviation; TNF, tumor necrosis factor.

Figure 7 Forest plot of the comparison of adverse effects.

Note: The random-effects meta-analysis model (Mantel–Haenszel method) was used in this analysis.
Abbreviations: 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.

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