| Autor: |
Hosoi, Hayato, Ikeda, Hiroaki, Imai, Naoko, Amaike, Chisaki, Wang, Linan, Orito, Yuki, Yamane, Makiko, Ueno, Hiroaki, Ideno, Mitsuko, Nukaya, Ikuei, Enoki, Tatsuji, Mineno, Junichi, Takesako, Kazutoh, Hirano, Satoshi, Shiku, Hiroshi |
| Zdroj: |
European Journal of Immunology; Jun2014, Vol. 44 Issue 6, p1747-1758, 12p |
| Abstrakt: |
T cells express multiple integrin molecules. The significance of signaling through these molecules on acquisition of T-cell effector functions and memory formation capacity remains largely unknown. Moreover, the impact of stimulation through these signals on the generation of T cells for adoptive immunotherapy has not been elucidated. In this study, using a recombinant fragment of fibronectin, CH-296, we demonstrated that stimulation via very late Ag (VLA)-4 and VLA-5 in human and BALB/c mouse CD8+ T cells, in combination with TCR stimulation, enhances effector multifunctionality and in vivo memory formation. Using TCR-transgenic mouse-derived CD8+ T cells expressing TCR specific for the syngeneic CMS5 fibrosarcoma-derived tumor Ag, we showed that stimulation by CH-296 improved the ability of tumor-specific CD8+ T cells to inhibit CMS5 tumor growth when adoptively transferred into hosts with progressing tumors. Improved antitumor effects were associated with decreased infiltration of Foxp3+CD4+ Treg cells in tumors. These results suggest that stimulation via VLA-4 and VLA-5 modulates the qualities of effector T cells and could potentially increase the efficacy of adoptive therapy against cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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