Department of Microbiology, Immunology, and Cancer Biology at the Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
J Neuroimmunol. 2024 Aug 15;393:578402. doi: 10.1016/j.jneuroim.2024.578402. Epub 2024 Jul 8.
Few T cells infiltrate into primary brain tumors, fundamentally hampering the effectiveness of immunotherapy. We hypothesized that Toxoplasma gondii, a microorganism that naturally elicits a Th1 response in the brain, can promote T cell infiltration into brain tumors despite their immune suppressive microenvironment. Using a mouse genetic model for medulloblastoma, we found that T. gondii infection induced the infiltration of activatable T cells into the tumor mass and led to myeloid cell reprogramming toward a T cell-supportive state, without causing severe health issues in mice. The study provides a concrete foundation for future studies to take advantage of the immune modulatory capacity of T. gondii to facilitate brain tumor immunotherapy.
少量 T 细胞浸润原发性脑肿瘤,从根本上阻碍了免疫疗法的效果。我们假设,弓形虫是一种微生物,它在大脑中自然引发 Th1 反应,即使在肿瘤具有免疫抑制微环境的情况下,也能促进 T 细胞浸润脑肿瘤。我们使用一种用于髓母细胞瘤的小鼠遗传模型发现,弓形虫感染诱导激活的 T 细胞浸润肿瘤块,并导致髓样细胞向有利于 T 细胞支持状态的重编程,而不会在小鼠中引起严重的健康问题。该研究为未来利用弓形虫的免疫调节能力促进脑肿瘤免疫疗法的研究提供了具体的基础。