Inflammatory cytokines presented from polymer matrices differentially generate and activate DCs in situ.
Inflammatory cytokines presented from polymer matrices differentially generate and activate DCs in situ.
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DOI：
10.1002/adfm.201203859
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发表时间：
2013-08-01
影响因子：
19
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Ali, Omar A.;Tayalia, Prakriti;Shvartsman, Dmitry;Lewin, Sarah;Mooney, David J.
During infection, inflammatory cytokines mobilize and activate dendritic cells (DCs), which are essential for efficacious T cell priming and immune responses that clear the infection. Here we designed macroporous poly(lactide-co-glycolide) (PLG) matrices to release the inflammatory cytokines GM-CSF, Flt3L and CCL20, in order to mimic infection-induced DC recruitment. We then tested the ability of these infection mimics to function as cancer vaccines via induction of specific, anti-tumor T cell responses. All vaccine systems tested were able to confer specific anti-tumor T cell responses and longterm survival in a therapeutic, B16-F10 melanoma model. However, GM-CSF and Flt3L vaccines resulted in similar survival rates, and outperformed CCL20 loaded scaffolds, even though they had differential effects on DC recruitment and generation. GM-CSF signaling was identified as the most potent chemotactic factor for conventional DCs and significantly enhanced surface expression of MHC(II) and CD86(+), which are utilized for priming T cell immunity. In contrast, Flt3L vaccines led to greater numbers of plasmacytoid DCs (pDCs), correlating with increased levels of T cell priming cytokines that amplify T cell responses. These results demonstrate that 3D polymer matrices modified to present inflammatory cytokines may be utilized to effectively mobilize and activate different DC subsets in vivo for immunotherapy.
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影响因子：
5.5
作者：
Hansen, Morten;Hjorto, Gertrud Malene;Svane, Inge Marie
通讯作者：
Svane, Inge Marie
影响因子：
15.3
作者：
Dieu, M C;Vanbervliet, B;Vicari, A;Bridon, J M;Oldham, E;Ait-Yahia, S;Briere, F;Zlotnik, A;Lebecque, S;Caux, C
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32.4
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2.2
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Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G
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14
作者：
Bennewitz, NL;Babensee, JE
通讯作者：
Babensee, JE