Songlei Zhou, Yukun Huang, Yu Chen, Yipu Liu, Laozhi Xie, Yang You, Shiqiang Tong, Jianpei Xu, Gan Jiang , Qingxiang Song, Ni Mei,Fenfen Ma, Xiaoling Gao , Hongzhuan Chen & Jun Chen
January 26, 2023
The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immuno- suppression. Here, we develop a nanostructure named Nano-reshaper to co- encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.
Zhou, S., Huang, Y., Chen, Y., Liu, Y., Xie, L., You, Y., … & Chen, J. (2023). Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma. Nature Communications, 14(1), 435.