Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Vaccine. 2018 Dec 18;36(52):8148-8157. doi: 10.1016/j.vaccine.2018.04.053. Epub 2018 Nov 16.
The adjuvant effects of flagellin on regulation of immune response have been proved; whether flagellin could assist tumor cell lysate (TCL) to enhance anti-glioma immunity remains to be investigated. This study tests a hypothesis that therapeuticly intracranial administration with flagellin plus TCL enhances the effects of specific immunotherapy on glioma in mice. In this study, GL261 cells were transferred into C57BL/6 mice and the GL261-bearing mice were subcutaneously or intracranially inoculated with flagellin plus TCL, flagellin, TCL or saline. Our results showed that prophylacticly subcutaneous administration with TCL and flagellin could induce potent cytotoxic T lymphocyte (CTL) and prolong the survival of GL261-bearing mice significantly, but therapeuticly subcutaneous administration failed to. However, therapeuticly intracranial administration of TCL plus flagellin could prolong the survival. Moreover, intracranial administration of flagellin could recruit CD4 T cells and CD8 T cells to brain tissues, induce proliferation of natural killer (NK) cells, CD4 T cells and CD8 T cells in peripheral blood mononuclear cells and induce to splenomegaly. The results suggested that flagellin could be acted as an efficient adjuvant for TCL based vaccine.
鞭毛蛋白在调节免疫反应方面的佐剂作用已得到证实；鞭毛蛋白是否能辅助肿瘤细胞裂解物（TCL）增强抗神经胶质瘤免疫仍有待研究。本研究检验了一个假设，即通过鞭毛蛋白联合 TCL 进行治疗性颅内给药可增强针对小鼠神经胶质瘤的特异性免疫治疗效果。在这项研究中，将 GL261 细胞转移到 C57BL/6 小鼠中，并通过皮下或颅内接种鞭毛蛋白联合 TCL、鞭毛蛋白、TCL 或生理盐水来接种 GL261 细胞。我们的结果表明，预防性皮下给予 TCL 和鞭毛蛋白可诱导强烈的细胞毒性 T 淋巴细胞（CTL），并显著延长 GL261 荷瘤小鼠的存活期，但治疗性皮下给予则无效。然而，治疗性颅内给予 TCL 联合鞭毛蛋白可延长生存期。此外，颅内给予鞭毛蛋白可招募 CD4 T 细胞和 CD8 T 细胞到脑组织中，诱导外周血单个核细胞中自然杀伤（NK）细胞、CD4 T 细胞和 CD8 T 细胞的增殖，并诱导脾肿大。这些结果表明，鞭毛蛋白可作为 TCL 疫苗的有效佐剂。
