口腔医学研究

口腔医学研究 ›› 2026, Vol. 42 ›› Issue (6): 512-518.DOI: 10.13701/j.cnki.kqyxyj.2026.06.009

• 口腔颌面外科学研究 • 上一篇    下一篇

西妥昔单抗促进自然杀伤细胞对口腔鳞状细胞癌类器官杀伤性的初步研究

刘丰1,2, 朱梦宇1,2, 陈霖2, 郑璐茜2,3, 杨昊楠1,2, 戴雨薇1,2, 孟箭1,2,3*   

  1. 1.山东第二医科大学口腔医学院 山东 潍坊 261000;
    2.徐州市中心医院口腔科 江苏 徐州 221000;
    3.徐州医科大学徐州临床学院 江苏 徐州 221000
  • 收稿日期:2025-10-16 出版日期:2026-06-28 发布日期:2026-06-23
  • 通讯作者: *孟箭,E-mail:mrocket@126.com
  • 作者简介:刘丰(1999~),女,山东人,硕士在读,主要从事口腔颌面外科相关研究。
  • 基金资助:
    江苏省老年健康科研面上项目(编号:LKM2024031);徐州市“卫生登峰”团队培养项目(编号:2025DF08)

Preliminary Study on Cetuximab Enhancing Cytotoxicity of Natural Killer Cells Against Oral Squamous Cell Carcinoma Organoids

LIU Feng1,2, ZHU Mengyu1,2, CHEN Lin2, ZHENG Luxi2,3, YANG Haonan1,2, DAI Yuwei1,2, MENG Jian1,2,3*   

  1. 1. School of Stomatology, Shandong Second Medical University, Weifang 261000, China;
    2. Department of Stomatology, Xuzhou Central Hospital, Xuzhou 221000, China;
    3. Xuzhou Clinical College, Xuzhou Medical University, Xuzhou 221000, China
  • Received:2025-10-16 Online:2026-06-28 Published:2026-06-23

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摘要： 目的:构建患者源性口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)类器官(patient-derived organoid,PDO)模型与外周血自然杀伤(natural killer,NK)细胞共培养体系,探究NK细胞联合西妥昔单抗(Cetuximab)对OSCC的杀伤效应,为OSCC免疫联合靶向治疗提供临床前依据。方法:体外构建35例OSCC患者的PDO,分离35例健康志愿者外周血NK细胞,经形态学、免疫组织化学检测(immunohistochemistry,IHC)及流式细胞术进行鉴定。构建OSCC PDO-NK细胞共培养模型,分别加入不同浓度的西妥昔单抗(12.5、25、50、100、200、400 μg/mL)。用CCK-8法检测OSCC PDO活力、流式细胞术分析其凋亡。结果:成功构建28例OSCC PDO,其形态学与分子标志物的表达与原发肿瘤高度一致。成功分离NK细胞并建立共培养模型。与PDO单独培养组相比,NK细胞共培养组PDO生长显著抑制,且效靶比越高杀伤效应越强。联合西妥昔单抗处理后,PDO凋亡率明显升高,提示药物与NK细胞存在协同促凋亡效应。结论:西妥昔单抗可协同增强NK细胞对OSCC PDO的细胞毒作用,其机制可能与抗体依赖的细胞介导的细胞毒作用(antibody-dependent cellular cytotoxicity,ADCC)相关。本研究可为晚期OSCC免疫联合靶向治疗提供实验依据。

关键词: 口腔鳞状细胞癌, 患者源性类器官, 自然杀伤细胞, 西妥昔单抗, 共培养

Abstract: Objective: To establish a co-culture system of patient-derived organoids (PDOs) from oral squamous cell carcinoma (OSCC) and peripheral blood natural killer (NK) cells, and to explore the cytotoxic effects of NK cells combined with Cetuximab on OSCC, providing preclinical evidence for immunotherapy combined with targeted therapy. Methods: PDOs were established in vitro from 35 OSCC patients, and NK cells were isolated from peripheral blood of 35 healthy volunteers. Both cell types were identified by morphology, immunohistochemistry (IHC), and flow cytometry. A co-culture model of OSCC PDOs and NK cells was established, with different concentrations of Cetuximab (12.5, 25, 50, 100, 200, and 400 μg/mL). The viability of PDOs was detected using the CCK-8, and apoptosis was analyzed by flow cytometry. Results: Twenty-eight OSCC PDOs were successfully established, showing high consistency with primary tumors in morphology and molecular markers. Compared with the PDO monoculture group, the co-culture group with NK cells significantly inhibited PDO growth, and the cytotoxicity increased with the effector-to-target ratio. Cetuximab combined with NK cells significantly enhanced PDO apoptosis, suggesting a synergistic pro-apoptotic effect. Conclusion: Cetuximab synergistically enhances the cytotoxicity of NK cells against OSCC PDOs, possibly through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. This study provides a theoretical and experimental basis for combined immunotherapy and targeted therapy in advanced OSCC.

Key words: oral squamous cell carcinoma, patient-derived organoid, natural killer cell, Cetuximab, co-culture