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干扰素-α 增强 NK 细胞功能以对抗自体血小板介导的肿瘤免疫逃逸

英文原题:Interferon-α enhances NK cell function to counteract autologous platelet-mediated tumor immune evasion.

查看英文原题

Interferon-α enhances NK cell function to counteract autologous platelet-mediated tumor immune evasion.

PubMed 2026/01/23(内容时间) Cancer Cell Int Q1 · IF 7(JCR 2025)

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研究概要

我们的研究揭示,自体血小板会削弱 NK 细胞介导的抗肿瘤反应,但这种抑制可通过 IFN- 治疗得以克服。

中文摘要

自然杀伤(NK)细胞是先天免疫系统的细胞防御组分,在抗肿瘤免疫中发挥重要作用。随着NK细胞疗法日益受到癌症治疗领域关注,有必要评估潜在负面干扰和不良相互作用。血小板虽已被认为可调节肿瘤免疫,但在个体化医疗背景下,自体血小板对NK细胞功能的影响尚未充分研究。

为探究自体血小板对NK细胞活性的调节作用,我们使用34名健康供者的新鲜血样建立新型评估平台(女性25名、男性9名;平均年龄28.29±6.25岁)。对是否预先接受IFN-γ刺激的NK细胞,在有或无自体血小板的情况下与K562白血病细胞共培养,评估功能应答。

NK细胞可通过释放IFN-γ等细胞因子介导抗肿瘤免疫,也可通过细胞毒性颗粒直接清除肿瘤细胞。在共培养系统中,血小板抑制NK细胞产生IFN-γ和细胞毒性脱颗粒,导致肿瘤细胞杀伤受损。值得注意的是,IFN-γ处理可有效逆转这一抑制,在所有受试供者中恢复NK细胞细胞毒功能和细胞因子应答。

本研究表明,自体血小板会损害NK细胞介导的抗肿瘤应答,但IFN-γ处理可克服这种抑制。我们建立的评估平台可用于研究血小板—NK细胞—肿瘤之间的相互作用,也可作为筛选免疫调节剂和定制NK细胞疗法的有用模型。

展开英文摘要原文

Natural Killer (NK) cells, a cellular defense component of the innate immune system, play a vital role in anti-tumor immunity. As interest in NK cell-based therapies grows within the field of cancer treatment, assessing potential negative interferences and adverse interactions is essential. Although platelets are recognized as modulators of tumor immunity, the impact of autologous platelets on NK cell function remains insufficiently explored in the realm of personalized medicine.

To investigate the role of autologous platelets in modulating NK cell activity, we developed a novel assessment platform using fresh blood samples from 34 healthy donors (25 females, 9 males; mean age 28.29 6.25 years). NK cells, with or without prior IFN- stimulation, were co-cultured with K562 leukemia cells in the presence or absence of autologous platelets to assess functional responses.

NK cells can exert anti-tumor immunity by releasing cytokines like IFN- and directly eliminating tumor cells through cytotoxic granules. In our co-culture system, platelets demonstrated suppressive effects on NK cell IFN- production and cytotoxic degranulation, resulting in impaired tumor cell killing. Notably, this suppression was effectively reversed by IFN- treatment, which restored NK cell cytotoxic function and cytokine responses in all donors tested.

Our study reveals that autologous platelets compromise NK cell-mediated anti-tumor responses, but this suppression can be overcome with IFN- treatment. The assessment platform we introduced provides a practical tool to study platelet NK tumor interactions and serves as a valuable model for screening immunomodulatory agents and tailoring NK cell-based therapies.

论文信息

作者
Wang LT、Shih CC、Chen YH、Chang CF、Fan HL、Chen TW、Chen YW、Krupalakshmi S
第一作者单位
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.Taiwan
通讯作者单位
Division of Gastroenterology, Department of Internal Medicine, Tri- Service General Hospital, National Defense Medical University, Taipei, Taiwan. weichen@mail.ndmctsgh.edu.tw.Taiwan
期刊
Cancer cell international2026 Jan 23
原文标识
PubMed 41578270 · DOI 10.1186/s12935-025-04118-w