Safety and efficacy of cytokine-induced killer cells for gastric cancer: a systematic review and meta-analysis.

Background: Cytokine-induced killer cell (CIK) cell therapy shows promising antitumor effects in gastric cancer (GC). Given variability in clinical outcomes across studies, a systematic review and meta-analysis was conducted to assess overall safety and efficacy. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for studies evaluating the safety and efficacy of CIK/dendritic cell-cytokine-induced killer cell (DC-CIK) cell therapy in gastric cancer. Time-to-event outcomes (OS, DFS, PFS) were synthesized using hazard ratios (HRs); fixed time-point survival effects from 6 months to 5 years were additionally summarized in supplementary analyses. Fixed- or random-effects models were applied as appropriate. Publication bias was examined using Begg's test and funnel plots, and robustness was explored with the Trim-and-Fill method. Safety and secondary outcomes (e.g., adverse events and T-lymphocyte subsets) were summarized descriptively. Results: A total of 22 trials including 2,149 patients were included. After risk-of-bias assessment, 13 studies were included in the quantitative synthesis. Pooled HRs showed significant benefits of CIK/DC-CIK plus chemotherapy compared with chemotherapy alone: OS (9 studies; 1,047 patients) HR 0.60 (95% CI 0.48-0.75; p<0.001), PFS (4 studies; 418 patients) HR 0.60 (95% CI 0.46-0.77; p<0.001), and DFS (4 studies; 523 patients) HR 0.70 (95% CI 0.58-0.86; p<0.001). ORR showed a non-significant trend in favor of CIK/DC-CIK (3 studies; 225 patients; pooled log OR 0.46, 95% CI -0.07 to 0.99; p=0.09), while DCR was significantly improved (3 studies; 225 patients; pooled log OR 0.81, 95% CI 0.17 to 1.45; p=0.01). Immunological analyses showed increased CD3+, CD4+, and CD4+/CD8+ T cells, with a slight decrease in CD8+ cells. Fever was the most frequently reported infusion-related adverse event, and no fatal adverse events were reported; however, grade ≥3 adverse events were inconsistently reported and could not be pooled, limiting certainty regarding comparative safety. No geographic restriction was applied; however, all identified eligible studies were conducted in China. Conclusion: Based on available studies, CIK/CIK-DC immunotherapy combined with chemotherapy significantly improves OS, PFS, and DFS in patients with gastric cancer and increases the DCR, without inducing severe adverse effects. Although these findings suggest potential benefit, validation in more diverse populations is needed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251160258.