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刚地弓形虫来源的外泌体:一种优于刚地弓形虫的潜在免疫刺激剂和肿瘤免疫治疗递送系统。

Toxoplasma gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma gondii.

机构信息

College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, 230032, People's Republic of China.

Department of Stomatology, Anhui Province Direct Subordinate Hospital, Hefei, 230601, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Nov 22;19:12421-12438. doi: 10.2147/IJN.S483626. eCollection 2024.

Abstract

Immunotherapies such as immune checkpoint blockade (ICB) therapy and chimeric antigen receptor T-cell (CAR-T) therapy have ushered in a new era of tumor treatment. However, most patients do not benefit from immunotherapy due to limitations such as narrow indications, low response rates, and high rates of adverse effects. (), a specialized intracellular protozoan, can modulate host immune responses by inhibiting or stimulating cytokines. The ability of to enhance an organism's immune response was found to have a direct anti-tumor effect and enhance the sensitivity of patients with tumors to ICB therapy. However, the application of for tumor therapy faces several challenges, such as biosafety concerns. Exosomes, a subtype of extracellular vesicle that contains active components such as proteins, nucleic acids, and lipids, have become effective therapeutic tools for various diseases, including tumors. Parasites, such as , mediate the communication of pathogens with immune cells and modulate host cellular immune responses through exosomes. Growing evidence indicates that -derived exosomes mediate communication between pathogens and immune cells, modulate host immune responses, and have great potential as new tools for tumor therapy. In this review, we highlight recent advances in isolation and identification techniques, profiling analysis, host immunomodulatory mechanisms, and the role of -derived exosomes in tumor immunotherapy. Additionally, we emphasize the potential of -derived exosomes as delivery platform to enhance anti-tumor efficacy in combination with other therapies. This review proposes that T. gondii-derived exosomes may serve as a novel tool for tumor immunotherapy owing to their ability to activate host immune function and properties such as high modifiability, stability, and low toxicity. This work will assist in promoting the application of parasite exosomes in tumor therapy.

摘要

免疫疗法,如免疫检查点阻断 (ICB) 疗法和嵌合抗原受体 T 细胞 (CAR-T) 疗法,开创了肿瘤治疗的新时代。然而,由于适应证狭窄、反应率低和不良反应率高,大多数患者无法从免疫疗法中获益。弓形虫()是一种专门的细胞内原生动物,通过抑制或刺激细胞因子来调节宿主免疫反应。发现弓形虫增强生物体免疫反应的能力具有直接的抗肿瘤作用,并增强肿瘤患者对 ICB 治疗的敏感性。然而,弓形虫用于肿瘤治疗的应用面临着一些挑战,如生物安全性问题。外泌体是一种包含蛋白质、核酸和脂质等活性成分的细胞外囊泡亚类,已成为包括肿瘤在内的各种疾病的有效治疗工具。寄生虫,如弓形虫,通过外泌体介导病原体与免疫细胞的通讯,并调节宿主细胞免疫反应。越来越多的证据表明,弓形虫衍生的外泌体介导病原体与免疫细胞之间的通讯,调节宿主免疫反应,并且作为肿瘤治疗的新工具具有巨大的潜力。在这篇综述中,我们强调了分离和鉴定技术、特征分析、宿主免疫调节机制以及弓形虫衍生外泌体在肿瘤免疫治疗中的作用的最新进展。此外,我们强调了弓形虫衍生外泌体作为递送平台与其他疗法联合增强抗肿瘤疗效的潜力。鉴于其激活宿主免疫功能的能力以及可修饰性高、稳定性好、毒性低等特性,本综述提出弓形虫衍生外泌体可能成为肿瘤免疫治疗的一种新工具。这项工作将有助于促进寄生虫外泌体在肿瘤治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dcf/11590659/978ebc16f571/IJN-19-12421-g0001.jpg

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