Table 2.
Main findings and level of evidence reported in meta-analyses of adoptive cell immunotherapy for cancer.
| Author, Year | Comparison | Cancer Type | RCT n. | Intervention /Control |
Outcome | Metrics | R/N/S † | R p-Value |
R SE (95% CI) |
I2(%) | 95% Prediction Interval | Egger p-Value |
Excess Significance | Level of Evidence |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dendritic cells with cytokine-induced killer cells | ||||||||||||||
| Su et al. 2016 | DC/CIK vs obs with backbone TACE | HCC | 5 | 250/245 | DCR | OR | 0/3/2 | 0.033 | 1.84 (1.05–3.24) |
18 | 0.35–9.60 | 0.55 | p > 0.1 | Suggestive |
| Su et al. 2016 | DC/CIK vs obs with backbone TACE | HCC | 3 | 104/106 | 1-year OS | OR | 0/3/0 | 0.027 | 2.00 (1.08–3.70) |
0 | 0.04–107.12 | 0.12 | p > 0.1 | Weak |
| Wang et al. 2015 | DC/CIK + CT vs CT | NSCLC | 5 | 191/192 | PFS | HR | 0/2/3 | <0.001 | 0.53 (0.39–0.71) |
0 | 0.32–0.86 | 0.76 | p > 0.1 | Suggestive |
| Zheng et al. 2015 | DC/CIK + CTx vs CTx | NSCLC | 3 | 141/141 | DCR | RR | 0/1/2 | 0.007 | 1.26 (1.07–1.50) |
10 | 0.36–4.47 | 0.22 | p > 0.1 | Suggestive |
| DC/CIK NSCLC OS|| | DC/CIK + CT vs CT | NSCLC | 10 | 387/427 | Longest OS reported | RR | 0/7/3 | <0.001 | 0.82 (0.75–0.89) |
0 | 0.74–0.90 | 0.19 | p > 0.1 | Suggestive |
| Lan et al. 2015 | DC/CIK + CTx vs CTx | Solid tumor, NSCLC or rectal cancer or colorectal cancer or colon cancer or breast cancer or gastric cancer | 5 | 195/202 | 3-year OS | OR | 0/4/1 | 0.007 | 0.37 (0.18–0.77) |
35 | 0.06–2.51 | 0.28 | p > 0.1 | Suggestive |
| Lan et al. 2015 | DC/CIK + CTx vs CTx | Solid tumor, NSCLC or rectal cancer or colorectal cancer or colon cancer or breast cancer or gastric cancer | 6 | 207/224 | Overall response | OR | 0/5/1 | 0.005 | 0.54 (0.35–0.83) |
0 | 0.30–0.99 | 0.36 | p > 0.1 | Suggestive |
| Cytokine-induced killer cells | ||||||||||||||
| Li et al. 2016 | Adjuvant CIK vs no AT | Treated HCC, Barcelona-clinic liver cancer B or earlier stage | 7 | 460/405 | PFS | RR | 0/5/2 | 0.004 | 0.76 (0.63–0.91) |
66 | 0.45–1.29 | 0.02 | p > 0.1 | Weak |
| Li et al. 2016 | Adjuvant CIK vs no AT | Treated HCC, Barcelona-clinic liver cancer B or earlier stage | 5 | 380/335 | OS | RR | 0/3/2 | 0.021 | 0.78 (0.64–0.96) |
42 | 0.44–1.39 | 0.04 | p > 0.1 | Weak |
| Wang et al. 2016 | CIK vs no AT after resection | Resected HCC | 5 | 402/357 | 3-year OS | RR | 0/5/0 | 0.010 | 1.15 (1.03–1.28) |
0 | 0.97–1.36 | 0.91 | p > 0.1 | Weak |
| Wang et al. 2016 | CIK vs no AT after resection | Resected HCC | 5 | 402/357 | 3-year recurrence-free survival | RR | 0/4/1 | 0.007 | 1.33 (1.08–1.64) |
7 | 0.90–1.98 | 0.87 | p > 0.1 | Suggestive |
| Yu et al. 2017 | Adjuvant CIK + CT vs CT | HCC | 7 | 451/422 | OS | HR | 0/3/4 | <0.001 | 0.64 (0.51–0.82) |
50 | 0.34–1.23 | 0.25 | p > 0.1 | Suggestive |
| Other adoptive cellular immunotherapies | ||||||||||||||
| Yuan et al. 2017 | Postoperative ACI (CIK or LAK + IL-2 or lymphocytes) vs no AT | Pretreated HCC, not advanced | 6 | 407/362 | 3-year mortality | RR | 0/5/1 | 0.009 | 0.71 (0.55–0.92) |
0 | 0.49–1.02 | 0.81 | p > 0.1 | Suggestive |
| Yuan et al. 2017 | Postoperative ACI (CIK or LAK + IL-2 or lymphocytes) vs no AT | Pretreated HCC, not advanced | 6 | 407/362 | 3-year recurrence rate | RR | 0/5/1 | 0.001 | 0.81 (0.72–0.92) |
0 | 0.68–0.97 | 0.30 | p > 0.1 | Suggestive |
| Zeng et al. 2016 | Postoperative ACI (AKT-DC or DC/CIK or LAK + IL-2 or TIL + rIL-2) + CT vs CT | Resected NSCLC | 4 | 234/238 | OS | HR | 0/3/1 | 0.013 | 0.59 (0.39–0.89) |
40 | 0.14–2.56 | 0.16 | p > 0.1 | Suggestive |
| Zhao et al. 2017 | ACI (LAK + IL-2 or DC/CIK or CIK or AKT or TIL) vs CT | NSCLC, operated or non-operated | 11 | 669/755 | 2-year OS | RR | 0/5/6 | <0.001 | 1.43 (1.30–1.58) |
0 | 1.28–1.61 | 0.24 | p > 0.1 | Convincing |
| Zhao et al. 2017 | ACI (LAK + IL-2 or DC/CIK or CIK or AKT or TIL) vs CT | NSCLC, operated or non-operated | 8 | 529/613 | 3-year OS | RR | 0/5/3 | <0.001 | 1.45 (1.24–1.69) |
0 | 1.19–1.76 | 0.31 | p > 0.1 | Suggestive |
| Zhao et al. 2017 | ACI (LAK + IL-2 or DC/CIK or CIK or AKT or TIL) vs CT | NSCLC, operated or non-operated | 4 | 187/229 | 1-year PFS | RR | 0/2/2 | 0.031 | 1.46 (1.24–1.72) |
0 | 1.02–2.09 | 0.16 | p > 0.1 | Suggestive |
| Tang et al. 2013 | ACI (autolymphocyte or LAK or CIK) vs no ACI | Metastatic RCC | 4 | 235/224 | 1-year OS | RR | 0/3/1 | <0.001 | 1.33 (1.15–1.54) |
0 | 0.97–1.83 | 0.205 | p > 0.1 | Suggestive |
Abbreviations: RCT, randomized controlled trial; n., number; SE, standard effect; CI, confidence interval; M, model; F, fixed effect; R, random effect; NA, not available; C, concordance with largest study; Y, concordant with largest study; N, not concordant with largest study; OS, overall survival; PFS progression-free survival; RR, risk ratio; HR, hazard ratio; OR, odds ratio; TACE, Transcatheter arterial chemoembolization; CT, conventional therapy; CTx, chemotherapy; AT, adjuvant therapy; ACI, adoptive cell immunotherapy; CIK, cytokine-induced killer cells; LAK, lymphokine-activated killer cells; IL-2, Interleukin-2; DC/CIK, dendritic cells with cytokine-induced killer cells; AKT, activated killer T-cells; TIL, tumor-infiltrating lymphocytes; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; RCC, renal cell cancer. † Number of individual studies of effect size with statistically significant direction in favor of control therapy/not statistically significant/statistically significant in favor of immunotherapy. ||Re-analysis was performed on RCTs from all eligible meta-analyses we found. References are provided in the Reference Appendix of the Supplementary Materials. All p-Values are two-sided.