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GK-1 增强了负载 MAGE-AX 的骨髓树突状细胞在黑色素瘤小鼠中诱导的免疫应答。

GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

机构信息

Laboratorio de Inmunoterapia e Ingeniería de Tejidos, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Edificio A, Sexto Piso, Ciudad Universitaria, Avenida Universidad No. 3000, Ciudad de México 04510DF, Mexico.

出版信息

J Immunol Res. 2014;2014:158980. doi: 10.1155/2014/158980. Epub 2014 Oct 29.

DOI:10.1155/2014/158980
PMID:25759825
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4230216/
Abstract

The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

摘要

树突状细胞 (DC) 疫苗接种在癌症中的目的是诱导可能减少和控制肿瘤体积的肿瘤特异性效应 T 细胞。为了产生持久的肿瘤免疫反应，有必要找到能够驱动所需免疫反应的免疫刺激剂。来自阔节裂头绦虫的 GK-1 肽不仅诱导 DC 和 T 淋巴细胞共培养物中 TNFα、IFNγ 和 MCP-1 的产生增加，而且还具有针对流感病毒的免疫保护作用。此外，本研究的目的是将 GK-1 用作针对 MAGE 抗原的骨髓树突状细胞 (BMDC) 的免疫刺激剂；因此，BMDC 可用于治疗鼠黑色素瘤的免疫疗法。GK-1 在 BMDC 中诱导 CD86 和 IL-12 的显著增加。此外，使用 TNFα/GK-1/MAGE-AX 处理的 BMDC 诱导小鼠的存活率最高，肿瘤最小。此外，该治疗有助于增加淋巴结中 CD8 淋巴细胞的水平并产生 IFNγ。此外，组织病理学分析显示，用 GK-1/TNFα 处理并负载 MAGE-AX 的 BMDC 诱导肿瘤中出现更多凋亡和坏死区域，而未经治疗的小鼠则没有。这些结果突出了 GK-1 作为 DC 免疫刺激剂的特性，并表明该免疫疗法是治疗癌症的潜在候选方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/9721de35db0f/JIR2014-158980.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/97a85c46d9f6/JIR2014-158980.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/8cd3367a011f/JIR2014-158980.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/0bcb55d9b894/JIR2014-158980.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/5c8b64ccefd7/JIR2014-158980.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/9e8a33890fad/JIR2014-158980.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/9721de35db0f/JIR2014-158980.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/97a85c46d9f6/JIR2014-158980.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/8cd3367a011f/JIR2014-158980.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/0bcb55d9b894/JIR2014-158980.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/5c8b64ccefd7/JIR2014-158980.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/9e8a33890fad/JIR2014-158980.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cb/4230216/9721de35db0f/JIR2014-158980.006.jpg

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