Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

Nature Communications
Taisuke KondoAkihiko Yoshimura

Abstract

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM 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.

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Datasets Mentioned

BETA
GSE68003
GSE93211
GSE92381

Methods Mentioned

BETA
FACS
flow cytometry
transgenic
PMA
Feature extraction

Software Mentioned

stats package
frma
STAR
pcbcStats
Ensemble
Cufflinks
GraphPad Prism
ggplot2
stats
ComplexHeatmap

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