研究概要
本研究提示,西妥昔单抗、放疗与 NK 细胞联合的多模式方案可显著提高头颈部鳞状细胞癌(HNSCC)的治疗疗效,提供了一种新颖且有前景的治疗策略。
中文摘要
背景:头颈部鳞状细胞癌(HNSCC)预后不良,现有治疗因毒性高、生存率低而受限,凸显开发新疗法的必要性。自然杀伤(NK)细胞无需预先接触抗原即可识别并清除癌细胞。放疗可直接靶向肿瘤并提高肿瘤细胞活化配体表达,促进其与NK细胞相互作用。靶向EGFR的抗体西妥昔单抗可增强NK细胞细胞毒性。此外,抗PD-1抗体可通过阻断抑制信号进一步增强NK细胞功能。本研究旨在通过联合放疗、靶向治疗和扩增NK细胞,提高HNSCC治疗效果。
方法:从健康供者分离、活化并扩增NK细胞。将FaDu和SCC-47细胞系接种于NOD/SCID小鼠。小鼠接受PD-1抑制剂、西妥昔单抗和放疗治疗,随后静脉注射NK细胞。
结果:放疗提高了调节NK细胞敏感性的配体表达。西妥昔单抗、放疗和扩增NK细胞联合治疗显著抑制癌症进展并提高生存率。然而,加入抗PD-1抗体未进一步改善结局。
结论:本研究提示,西妥昔单抗、放疗和NK细胞组成的多模式疗法可显著提高HNSCC治疗效果,为治疗提供一种新型且有前景的策略。
展开英文摘要原文
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and current treatments are limited by high toxicity and low survival rates, highlighting the need for new therapeutic approaches. Natural killer (NK) cells can identify and eliminate cancer cells without prior antigen exposure. Radiotherapy directly targets tumors and increases activating ligands on tumor cells, promoting NK cell interactions. Cetuximab, an EGFR-targeting antibody, enhances NK cell cytotoxicity. Additionally, anti-PD-1 antibodies may further boost NK cell function by blocking inhibitory signals. The study aimed to enhance HNSCC treatment efficacy by combining radiotherapy and targeted therapy with expanded NK cells.
METHODS: NK cells were isolated, activated, and expanded from healthy donors. The FaDu and SCC-47 cell lines were inoculated into NOD/SCID mice. The mice were treated with PD-1 inhibitors, cetuximab, and radiation, followed by intravenous injection of NK cells.
RESULTS: Radiation increased ligands that regulate NK cell sensitivity. The combination of cetuximab, radiotherapy, and expanded NK cells significantly suppressed cancer progression and improved survival rates. However, adding anti-PD-1 antibodies did not further enhance outcomes.
CONCLUSION: This study suggests that a multimodal approach combining cetuximab, radiotherapy, and NK cells can significantly improve HNSCC therapy efficacy, offering a novel and promising treatment strategy.
论文信息
- 作者
- Son WC、Lee HR、Koh EK、Park GY、Kang HB、Song J、Ahn SY、Park YS
- 单位
- Department of Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, South Korea.South Korea
- 期刊
- Immunological investigations2025 Feb