Table S1. Characteristics of the included trials.
| Study (year) | Study design | Mean/median age, years, (range) | No. of participants (Im:control) | Hepatitis virus (%) | TNM stagea | BCLC stage | Regimen of the Im group | Regimen of the control group | Infusion of Im drug, times | Duration of Im drug, months | Dose per infusion of Im drugb |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Takayama et al. (24) (2000) | RCT | NR | 150 (76:74) | B (19.3%), C (66.0%) | I/II/IIIA/IIIB | A/B/C | Hr + ALT | Hr + Obs | 5 | 5.6 | 1.5×1010 |
| Weng et al. (33) (2008) | RCT | Median, Im: 55.4 (47.2–63.6), control: 56.4 (45.8–67) | 85 (45:40) | NR | I/II/IIIA | A/B/C | TACE + RFA + CIKT | TACE + RFA + Obs | 8 or 10 | <10 | 1.0×1010–1.5×1010 |
| Hui et al. (34) (2009) | RCT | NR | 127 (84:43) | B (75.6%) | I/II | A/B/C | Hr + CIKT | Hr + Obs | A: 3, B: 6 | A: 1.4, B: 2.8 | 1.0×1010–2.0×1010 |
| Yu et al. (20) (2014)c | RCT, phase II | NA | 82 (41:41) | B (NA) | I/II/IIIA | A/B/C | A: Hr + CIKT, B: TACE + CIKT | A: Hr + Obs, B: TACE + Obs | 72 | 36 | 5.1×109 |
| NCT00699816 (5) (2015) | RCT, phase III | Mean, Im: 43 (29.0–60.0), control: 45 (31.0–67.0) | 226 (114:112) | B (82.3%), C (8.4%), coinfection (1.8%) | I/II | A/B/C | A: Hr + CIKT, B: RFA + CIKT, C: PEI + CIKT | A: Hr + Obs, B: RFA + Obs, C: PEI + Obs | 16 | 14 | 6.4×109 |
| NCT00769106 (6) (2016) | RCT, phase III | Median, Im: 43 (38.0–56.0), control: 52 (43.0–60.0) | 200 (100:100) | B (85.5%) | I/II/IIIA | A/B/C | Hr + CIKT | Hr + Obs | 4 | 3 | 1.0×1010–1.5×1010 |
| Miyaguchi et al. (23) (2002) | RCT | Mean, Im: 66.2 (58.8–73.6), control: 65.0 (57.9–72.1) | 46 (22:24) | C (100%) | I/II | A/B | TACE + PEI + IFN-α | TACE + PEI | 52 | 4 | 3 |
| Shiratori et al. (26) (2003) | RCT | Median, Im: 61 (37.0–70.0), control: 63 (51.0–69.0) | 74 (49:25) | C (100%) | I/II | A/B/C | PEI + IFN-α | PEI + Obs | 144 | 11.2 | 6 |
| Lin et al. (30) (2004) | RCT | Median, Im: 61.5 (26.0–70.0), control: 59 (49.0–72.0) | 30 (20:10) | B (53.3%), C (46.7%) | I/II | A/B/C | A: PAIM + IFN-α, B: TACE + PAI + IFN-α | A: PAIM + placebo, B: TACE + PAI + placebo | Mean: 224, A: 309, B: 120 | 24 | 3 |
| Nishiguchi et al. (27) (2005) | RCT | Mean, Im: 61.9 (56.1–67.7), control: 60.0 (55.2–64.8) | 30 (15:15) | C (100%) | I | A | Hr + IFN-α | Hr + Obs | 232 | 24.3 | 6 |
| Sun et al. (25) (2006) | RCT | Median, 50 (20.0–77.0) | 236 (118:118) | B (100%) | I/II/IIIA | A/B/C | Hr + IFN-α | Hr + Obs | 232 | 18 | 5 |
| Lo et al. (29) (2007)c | RCT | NA | 41 (20:21) | B (≥95%) | I/II | A/B/C | Hr + IFN-α | Hr + Obs | 48 | 3.7 | 10 |
| Li et al. (31) (2009) | RCT | Median, 48 (20.0–73.0) | 216 (108:108) | B (100%) | I/II/IIIA | A/B/C | TACE + IFN-α | TACE | 135 | 11.2 | 3 |
| NCT00524498 (28) (2012) | RCT, phase II | Mean, Im: 64.0 (55.1–72.9), control: 65.5 (55.4–75.6) | 61 (30:31) | B (27.9%), C (47.5), alcoholic (14.8%) | IIIB | C | FAIT | FAIC | 12–48 | 1–3.7 | 5 |
| NCT00149565 (22) (2012) | RCT, phase III | Median, Im: 50 (48.0–54.0), control: 49 (46.0–51.0) | 268 (133:135) | B (80.2%), C (19.8%) | I/II/IIIA | A/B/C | Hr + IFN-α | Hr + Obs | 164 | 12.4 | 5 |
| Kuang et al. (21) (2004) | RCT, phase II | Mean, Im: 48 (39.0–57.0), control: 47 (34.0–60.0) | 39 (18:21) | B (89.7%), C (2.6%) | I/II/IIIA | A/B/C | Hr + AFTV | Hr + Obs | 3 | 1.4 | 40 µLd |
| KCT0000008 (32) (2017) | RCT, phase II | Mean, Im: 57.1 (47.6–66.6), control: 58.1 (47.3–68.9) | 144 (69:75) | B (72.2%), C (11.1%), coinfection (1.4%) | I/II/III | A/B/C | DCVT | Obs | 6 | 3.3 | 3×107 |
a, the tumor-node-metastasis staging of the tumors was determined according to the most recent American Joint Committee on Cancer staging system (8th edition); b, the unit of the dose for the cellular immunotherapy group and KCT0000008 was the cell count, and the unit for the cytokine immunotherapy group was million international units (MIU); c, patients with stage IV HCC were excluded from this study; d, the treatment dose included 40 µL of packed autologous formalin-fixed HCC fragments. AFTV, autologous formalin-fixed tumor vaccine; ALT, autologous lymphocyte therapy; BCLC, Barcelona Clinic Liver Cancer; CIKT, cytokine-induced killer therapy; DCVT, dendritic cell vaccine therapy; FAIC, 5-fluorouracil arterial infusion + cisplatin; FAIT, 5-fluorouracil arterial infusion + interferon therapy; Hr, hepatic resection; Im, immunotherapy; IFN-α, interferon-α therapy; NA, not applicable; NR, not reported; Obs, observation; PAI, percutaneous acetic acid injection; PAIM, percutaneous acetic acid injection monotherapy; PEI, percutaneous ethanol injection; RCT, randomized controlled trial; RFA, radiofrequency ablation; TACE, transcatheter arterial chemoembolization; TAE, transcatheter arterial embolization; TNM, tumor-node-metastasis; TVT, tumor vaccine therapy; OS, overall survival; and PFS, progression-free survival.