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弓形虫肌动蛋白结合蛋白样蛋白在小鼠自体全肿瘤细胞疫苗接种中的免疫佐剂作用

Immune adjuvant effect of a Toxoplasma gondii profilin-like protein in autologous whole-tumor-cell vaccination in mice.

作者信息

Pyo Kyoung-Ho, Lee You-Won, Lim Sun Min, Shin Eun-Hee

机构信息

Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea.

Current address: JE-UK Laboratory of Molecular Cancer Therapeutics, Yonsei Cancer Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Oncotarget. 2016 Nov 8;7(45):74107-74119. doi: 10.18632/oncotarget.12316.

DOI:10.18632/oncotarget.12316
PMID:27687589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5342039/
Abstract

Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs). In addition, TgPLP increased the phagocytosis of tumor cells by BMMs and promoted immune cell mobility on a tumor-matrigel scaffold. TgPLP triggered immune responses as demonstrated by increased expression of antigen presenting cell markers (MHC class I and II, B7.1, and B7.2) in BMMs and increased IL-12 and IFN-γ expression in mice. Mice vaccinated with AWV and TgPLP had more immune cells (CD4+ and CD8+ T cells, natural killer cells, and macrophages) in the spleen and higher total IgG and IgG2a concentrations in the blood than mice vaccinated with AWV alone. These findings suggest that TgPLP is a TLR-based vaccine adjuvant that enhances antitumor immune responses during vaccination with AWV.

摘要

弓形虫中的肌动蛋白结合蛋白样蛋白（TgPLP）是一种Toll样受体（TLR）激动剂。在本研究中，我们调查了TgPLP在自体全肿瘤细胞疫苗（AWV）治疗中对免疫功能是否具有佐剂作用。用AWV和重组TgPLP蛋白一起接种的小鼠CT26肿瘤较小，生存期延长。TgPLP处理通过MyD88信号通路强烈增加骨髓来源巨噬细胞（BMM）中IL-12以及包括CCL5、CCL12和XCL1在内的几种趋化因子的产生。此外，TgPLP增加了BMM对肿瘤细胞的吞噬作用，并促进了肿瘤基质胶支架上免疫细胞的迁移。TgPLP引发了免疫反应，表现为BMM中抗原呈递细胞标志物（MHC I类和II类、B7.1和B7.2）的表达增加以及小鼠中IL-12和IFN-γ表达增加。与仅接种AWV的小鼠相比，接种AWV和TgPLP的小鼠脾脏中有更多的免疫细胞（CD4 +和CD8 + T细胞、自然杀伤细胞和巨噬细胞），血液中的总IgG和IgG2a浓度更高。这些发现表明，TgPLP是一种基于TLR的疫苗佐剂，可在接种AWV期间增强抗肿瘤免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/3d7eaceea927/oncotarget-07-74107-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/eb4b83405804/oncotarget-07-74107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/371ba70a8953/oncotarget-07-74107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/f4ea62a07a6f/oncotarget-07-74107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/1ca1d7cbdb78/oncotarget-07-74107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/aecc17af802a/oncotarget-07-74107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/c95bbeb7354c/oncotarget-07-74107-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/c7cbdcbe88d8/oncotarget-07-74107-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/3d7eaceea927/oncotarget-07-74107-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/eb4b83405804/oncotarget-07-74107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/371ba70a8953/oncotarget-07-74107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/f4ea62a07a6f/oncotarget-07-74107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/1ca1d7cbdb78/oncotarget-07-74107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/aecc17af802a/oncotarget-07-74107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/c95bbeb7354c/oncotarget-07-74107-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/c7cbdcbe88d8/oncotarget-07-74107-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe4/5342039/3d7eaceea927/oncotarget-07-74107-g008.jpg

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