Pyo Kyoung-Ho, Lee You-Won, Lim Sun Min, Shin Eun-Hee
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.
Oncotarget. 2016 Nov 8;7(45):74107-74119. doi: 10.18632/oncotarget.12316.
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.
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。