Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28530241.
- Also identified by DOI 10.1038/ncomms15338 and PMC identifier 5458121.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T<sub>SCM</sub>) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8<sup>+</sup> T<sub>SCM</sub> cells can be generated in vitro from naive CD8<sup>+</sup> T cells via Wnt signalling; however, methods do not yet exist for inducing T<sub>SCM</sub> cells from activated or memory T cells. Here, we show a strategy for generating T<sub>SCM</sub>-like cells in vitro (iT<sub>SCM</sub> cells) from activated CD4<sup>+</sup> and CD8<sup>+</sup> T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT<sub>SCM</sub> cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.
Medical subject headings
- Immunotherapy, Adoptive
- Lymphocyte Activation
- Receptors, Notch
- T-Lymphocytes