Title | Human pluripotent stem cell-derived eosinophils reveal potent cytotoxicity against solid tumors |
Authors | Lai, Weifeng Xie, Huangfan Liu, Yuting Zheng, Feng Zhang, Yingfeng Lei, Qi Lv, Lejun Dong, Jiebin Song, Jian Gao, Xue Yin, Ming Wang, Chengyan Deng, Hongkui |
Affiliation | Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Sch Basic Med Sci, Beijing 100191, Peoples R China Peking Univ, MOE Key Lab Cell Proliferat & Differentiat, Coll Life Sci, Peking Tsinghua Ctr Life Sci, Beijing 100191, Peoples R China Peking Univ, Sch Life Sci, Ctr Bioinformat, Ctr Stat Sci, Beijing 100871, Peoples R China Beijing Vitalstar Biotechnol, Beijing 100012, Peoples R China |
Keywords | GENERATION INFILTRATION |
Issue Date | 13-Jul-2021 |
Publisher | STEM CELL REPORTS |
Abstract | Eosinophils are attractive innate immune cells to use to potentiate T cell antitumor efficacy because they are capable of infiltrating tumors at early stages and modulating the tumor microenvironment. However, the limited number of functional eosinophils caused by the scarcity and short life of primary eosinophils in peripheral blood has greatly impeded the development of eosinophil-based immunotherapy. In this study, we established an efficient chemically defined protocol to generate a large quantity of functional eosinophils from human pluripotent stem cells (hPSCs) with nearly 100% purity expressing eosinophil peroxidase. These hPSC-derived eosinophils transcriptionally resembled their primary counterpart. Moreover, hPSC-derived eosinophils showed competent tumor killing capacity in established solid tumors. Furthermore, the combination of hPSC-derived eosinophils with CAR-Tcells exhibited potential synergistic effects, inhibiting tumor growth and enhancing mouse survival. Our study opens up new avenues for the development of eosinophil-based immunotherapies to treat cancer. |
URI | http://hdl.handle.net/20.500.11897/619133 |
ISSN | 2213-6711 |
DOI | 10.1016/j.stemcr.2021.06.005 |
Indexed | SCI(E) |
Appears in Collections: | 医学部待认领 天然药物与仿生药物国家重点实验室 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 |