Adutler-Lieber, Shimrit Friedman, Nir Geiger, Benjamin image_2_Expansion and Antitumor Cytotoxicity of T-Cells Are Augmented by Substrate-Bound CCL21 and Intercellular Adhesion Molecule 1.tif <p>Adoptive immunotherapy is based on ex vivo expansion and stimulation of T-cells, followed by their transfer into patients. The need for the ex vivo culturing step provides opportunities for modulating the properties of transferred T-cells, enhancing their antitumor abilities, and increasing their number. Here, we present a synthetic immune niche (SIN) that increases the number and antitumor activity of cytotoxic CD8<sup>+</sup> T-cells. We first evaluated the effect of various SIN compositions that mimic the physiological microenvironment encountered by T-cells during their activation and expansion in the lymph node. We found that substrates coated with the chemokine CCL21 together with the adhesion molecule intercellular adhesion molecule 1 significantly increase the number of ovalbumin-specific murine CD8<sup>+</sup> T-cells activated by antigen-loaded dendritic cells or activation microbeads. Notably, cells cultured on these substrates also displayed augmented cytotoxic activity toward ovalbumin-expressing melanoma cells, both in culture and in vivo. This increase in specific cytotoxic activity was associated with a major increase in the cellular levels of the killing-mediator granzyme B. Our results suggest that this SIN may be used for generating T-cells with augmented cytotoxic function, for use in cancer immunotherapy.</p> CCL21;intercellular adhesion molecule 1;T-cell immunity;cancer immunotherapy;T-cell cytotoxicity;T-cell clusters 2018-06-11
    https://frontiersin.figshare.com/articles/figure/image_2_Expansion_and_Antitumor_Cytotoxicity_of_T-Cells_Are_Augmented_by_Substrate-Bound_CCL21_and_Intercellular_Adhesion_Molecule_1_tif/6477758
10.3389/fimmu.2018.01303.s002