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NK 细胞在呼吸系统肿瘤中的作用及其在治疗策略中的应用

英文原题:Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches.

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Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches.

PubMed 2024/11/01(内容时间) Immun Inflamm Dis Q2 · IF 3.5(JCR 2025)

研究概要

呼吸系统癌症在全球范围内构成重大健康挑战,而尽管 NK 细胞在肿瘤监视中发挥关键作用,肿瘤仍常通过多种机制逃逸 NK 细胞应答。

中文摘要

背景:癌症因其沉重的健康和社会经济负担,仍被视为全球重大健康问题。目前,肺癌是全球最常见的癌症相关死亡原因。间皮瘤及其他呼吸系统癌症,包括气管、喉和支气管癌,也构成重大健康威胁。自然杀伤(NK)细胞是先天免疫系统中的淋巴细胞,参与抗癌应答。 目的:本综述讨论NK细胞在呼吸系统癌症免疫监视中的作用,以及利用NK细胞治疗这些恶性肿瘤的研究进展。 结果:肿瘤微环境中存在NK细胞与多种恶性肿瘤患者较高生存率相关。然而,癌细胞能够通过多种机制逃避NK细胞介导的细胞毒作用,包括降低主要组织相容性复合体I类分子表达、脱落配体、上调抑制性受体以及释放可溶性因子。利用NK细胞设计治疗策略可能增强抗肿瘤免疫并改善临床结局。研究NK细胞联合细胞因子刺激或免疫检查点抑制剂治疗多种呼吸系统恶性肿瘤的临床试验已显示良好前景。 结论:呼吸系统癌症在全球造成重大健康挑战。NK细胞在肿瘤监视中发挥关键作用,但肿瘤常通过多种机制逃避NK细胞应答。包括CAR-NK细胞、免疫检查点抑制剂及细胞因子刺激在内的NK细胞疗法取得了良好进展;然而,免疫抑制性肿瘤微环境等挑战仍然存在。继续研究靶向自噬、调节miRNA及开发联合策略,对于增强呼吸系统癌症NK细胞疗法的疗效至关重要。

展开英文摘要原文

BACKGROUND: Cancer is still regarded as a major worldwide health issue due to its high health and socioeconomic burden. Currently, lung cancer is the most common cause of cancer-related fatalities globally. Additionally, mesotheliomas and other cancers of the respiratory system, including those of the trachea, larynx, and bronchi, are also posing a significant health threat. Natural killer (NK) cells are lymphocytes of the innate immune system involved in response against cancer. OBJECTIVE: This review discussed recent findings in the context of NK cell activity in the immune surveillance of respiratory system cancers and NK cell-based treatments to combat those malignancies. RESULTS: The presence of natural killer cells in the tumor microenvironment is shown to be associated with a higher survival rate in patients with various malignancies. However, cancerous cells benefit from several mechanisms to evade natural killer cell-mediated cytotoxicity, including reduced major histocompatibility complex I expression, shedding of ligands, upregulation of inhibitory receptors, and release of soluble factors. Using NK cells to design therapeutic approaches may enhance antitumor immunity and improve clinical outcomes. Clinical trials investigating the use of natural killer cells in combination with cytokine stimulation or immune checkpoint inhibitors have exhibited promising results in various respiratory system malignancies. CONCLUSION: Respiratory system cancers present significant health challenges worldwide, and while NK cells play a crucial role in tumor surveillance, tumors often evade NK cell responses through various mechanisms. Advances in NK cell-based therapies, including CAR-NK cells, immune checkpoint inhibitors, and cytokine stimulation, have shown promising outcomes in tackling these tactics. However, challenges such as the immunosuppressive tumor microenvironment persist. Ongoing research is crucial to improve NK cell therapies by targeting autophagy, modulating miRNAs, and developing combinatorial approaches to enhance treatment efficacy for respiratory cancers.

论文信息

作者
Dokhanchi M、Javaherdehi AP、Raad M、Khalilollah S、Mahdavi P、Razizadeh MH、Zafarani A
第一作者单位
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.Iran
通讯作者单位
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.Iran
文献类型
综述
期刊
Immunity, inflammation and disease2024 Nov
原文标识
PubMed 39588940 · DOI 10.1002/iid3.70079