TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination.
TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination.
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DOI：
10.4049/jimmunol.0900974
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发表时间：
2009-09-15
期刊：
影响因子：
--
通讯作者：
Dong H
中科院分区：
文献类型：
--
作者：
Pulko V;Liu X;Krco CJ;Harris KJ;Frigola X;Kwon ED;Dong H
TLR激动剂已被探索作为肿瘤免疫治疗的疫苗佐剂。然而，它们的免疫学后果尚不完全清楚。虽然TLR信号传导增加了树突状细胞（dc）启动T细胞的功能潜力，但潜在的负免疫调节能力的共同诱导可能会损害效应T细胞的产生。我们检测了B7家族共刺激分子在TLR3激动剂多肌苷：多胞酸激活后在DCs上的表达和功能。我们证明了多肌苷：多胞苷酸持续上调来自脾脏和淋巴结的常驻、迁移dc的B7-2和B7-H1分子。B7-H1在活化dc上的耗尽或阻断增加了效应CD8 T细胞扩增的幅度。基于dc或基于蛋白的肿瘤疫苗，结合B7-H1阻断，诱导强烈的效应CD8 T细胞反应，对新建立的肿瘤产生保护性免疫。我们的研究表明，TLR3信号可能上调apc上的正、负共调节分子。选择性阻断负调控分子联合TLR3激动剂可能是提高肿瘤疫苗疗效的有效策略。
Agonists of TLR have been explored as vaccine adjuvants for tumor immunotherapy. However, their immunological consequences are not fully understood. Although TLR signaling increases the functional potential of dendritic cells (DCs) for priming T cells, coinduction of potentially negative immunoregulatory capacities may impair effector T cell generation. We examined the expression and function of B7 family costimulatory molecules on DCs after activation with the TLR3 agonist, polyinosinic:polycytidylic acid. We demonstrated that polyinosinic:polycytidylic acid consistently up-regulated both B7-2 and B7-H1 molecules on resident, migratory DCs from spleen and lymph nodes. Depletion or blockade of B7-H1 on activated DCs increased the magnitude of effector CD8 T cell expansion. DC-based or protein-based tumor vaccines, in combination with B7-H1 blockade, induced strong effector CD8 T cell responses, resulting in protective immunity against newly established tumors. Our studies suggest that TLR3 signaling has the potential to up-regulate both positive and negative coregulatory molecules on APCs. Selective blockade of negative regulatory molecules in combination with TLR3 agonist may be an effective strategy for increasing the efficacy of tumor vaccines.
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影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
DOI：
10.1073/pnas.0712394105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Lin, Ming Lee;Zhan, Yifan;Lew, Andrew M.
通讯作者：
Lew, Andrew M.
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.4
作者：
Bellone, M;Cantarella, D;Dellabona, P
通讯作者：
Dellabona, P
DOI：
10.1084/jem.20031591
发表时间：
2004-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ahonen CL;Doxsee CL;McGurran SM;Riter TR;Wade WF;Barth RJ;Vasilakos JP;Noelle RJ;Kedl RM
通讯作者：
Kedl RM