The clinical application of T cell immunotherapy depends on ex vivo modification and expansion of T cells for adoptive transfer. In preclinical models, the use of a purified, naive T cell subset enhances persistence and antitumor immunity; however, the majority of clinical studies rely on modification of mixed populations of T cells that contain only a small subset of highly functional T cells with less-differentiated phenotype. In this month’s issue of the JCI, Klebanoff and colleagues uncover a Fas-mediated interaction between naive T cells and antigen-experienced T cells that drives differentiation and impairs adoptive immunotherapy. Further, they show that blockade of Fas signaling enhances antitumor immunity and increases survival in a mouse model of melanoma. Their work supports a growing body of evidence that the use of naive T cells enhances the efficacy of adoptive T cell therapy and suggests a new therapeutic strategy for preserving less-differentiated T cell populations.
Yang Xu, Gianpietro Dotti
Title and authors | Publication | Year |
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The Antitumor Effects of Vaccine-Activated CD8 + T Cells Associate with Weak TCR Signaling and Induction of Stem-Like Memory T Cells
S Wu, W Zhu, Y Peng, L Wang, Y Hong, L Huang, D Dong, J Xie, T Merchen, E Kruse, ZS Guo, D Bartlett, N Fu, Y He |
Cancer immunology research | 2017 |
Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
A Francian, K Mann, M Kullberg |
International Journal of Nanomedicine | 2017 |