CIK-augmented anti-PD1/CTLA4 immunotherapy eradicates chemo-resistant ovarian cancer via tripartite mechanistic synergy.

Background: Immune checkpoint inhibitors (ICIs) combined with adoptive cell therapy represent promising strategies against ovarian cancer, yet their synergistic mechanisms remain underexplored. This study evaluated the therapeutic efficacy of Nivolumab/Ipilimumab plus Cytokine-Induced Killer (CIK) cells in ovarian carcinoma models. Methods: Human ovarian cancer cells (A2780/SKOV3) were subjected to three treatment conditions: untreated controls, dual immune checkpoint inhibitors (ICIs: 4 μg/mL Nivolumab + 4 μg/mL Ipilimumab), or ICIs combined with CIK cells (5×104 cells/insert), with functional impacts evaluated through comprehensive assays including CCK-8 proliferation, transwell invasion, Annexin V-FITC/PI apoptosis detection, propidium iodide-based cell cycle analysis, and quantitative wound healing migration assessment. Results: The triple-combination therapy demonstrated synergistic efficacy, significantly reducing SKOV3 cell proliferation by 62.3% (P<0.001) and suppressing invasion capacity by 71.5% (P<0.01) in matrigel-transwell assays. Concurrently, it induced substantial apoptosis in A2780 cells (3.2-fold increase, 22.8% vs 7.1% control), triggered pronounced G0/G1 phase arrest in SKOV3 (55% vs 40% control) with concomitant S-phase depletion, and inhibited wound closure capacity by 64.7% in combinatorial treatment groups. Conclusion: The triple-combination therapy synergistically enhances antitumor efficacy through potent G1/S checkpoint blockade, selective cytotoxicity against ICI-resistant populations, and migration-inhibitory activity, thus establishing CIK-ICI coadministration as a clinically translatable strategy for advanced ovarian malignancies.