ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gynecological Oncology
This article is part of the Research TopicEvidence-Based Implementation of Innovations in Gynecological OncologyView all 3 articles
CIK-Augmented Anti-PD1/CTLA4 Immunotherapy Eradicates Chemo resistant Ovarian Tumors via Tripartite Mechanistic Synergy
Provisionally accepted
- Fujian Medical University Union Hospital, Fuzhou, China
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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.
Keywords: ovarian carcinoma, Combination immunotherapy, Cytokine-Induced Killer Cells, immune checkpoint inhibitors, Nivolumab, ipilimumab
Received: 21 Jul 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Chen, Pan, Chen and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiushan Feng, fengxiushan2004@126.com
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