期刊
CELL REPORTS
卷 22, 期 12, 页码 3175-3190出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.02.087
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资金
- Intramural Research Program of the National Cancer Institute [ZIA BC010763]
- NIH/NCI [K08CA197966]
- Tiens Charitable Foundation
- NIH Center for Regenerative Medicine
- Milstein Family Foundation
- Melanoma Research Alliance
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4(+) CD8(+) double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8 alpha beta(+) antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs). iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies.
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