| 10 | IRX-2, a novel biologic, favors the expansion of T effector over T regulatory cells in a human tumor microenvironment model显示文摘IRX-2, a natural cytokine biological with multiple components, has been used in preclinical and clinical studies to promote antitumor activity of T lymphocytes. To define cellular mechanisms responsible for antitumor effects of IRX-2, its ability to induce effector T cells( Teff) was examined in a model simulating the tumor microenvironment. An in vitro model containing conventional CD4+CD25 cells co-cultured with autologous immature dendritic cells, irradiated tumor cells, and cytokines was used to study differentiation and expansion of regulatory T cells(Treg) and Teff in the presence and absence of IRX-2. Phenotype, suppressor function, signaling, and cytokine production were serially measured using flow cytometry, Western blots, CFSE-based suppressor assays, and Luminex-based analyses. The presence of IRX-2 in the co-cultures promoted the induction and expansion of IFN- +Tbet+ Teff and significantly(p<0.01) decreased the induction of inducible IL-10+TGF-β+Treg. The responsible mechanism involved IFN-+-driven T cell polarization towards Teff and suppression of Treg differentiation.In an in vitro model simulating the human tumor microenvironment, IRX-2 promoted Teff expansion and antitumor activity without inducing Treg. Thus, IRX-2 could be considered as a promising component of future antitumor therapies. | Bastian Schilling Malgorzata Harasymczuk Patrick Schuler James E.Egan Theresa L.Whiteside | 2015 | 世界最新医学信息文摘2015，15，5： | 0 |
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