Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+) dendritic cells.
Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+) dendritic cells.
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通过选择性刺激先天DEC-205（+）树突状细胞，诱导肿瘤特异性获得的免疫力对已经建立的肿瘤。
DOI：
10.1007/s00262-010-0835-z
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发表时间：
2010-07
影响因子：
5.8
通讯作者：
Takahashi, Hidemi
中科院分区：
文献类型：
--
作者：
Moriya, Keiichi;Wakabayashi, Ayako;Shimizu, Masumi;Tamura, Hideto;Dan, Kazuo;Takahashi, Hidemi
在体内，树突状细胞(DC)的两个主要亚群被安排来调节我们的免疫反应：33D1+和DEC-205+DC。利用抗33D_1的单抗，成功地从C57BL/6小鼠体内清除了33D_1+DC。33D_1+DC耗竭小鼠经脂多糖刺激后，血清IL-12水平显著升高，但其余DEC-205+DC可能介导的IL-10分泌不明显，这可能导致Th1对TLR信号的支配作用。将同基因Hepa1-6肝癌细胞或B16-F10黑色素瘤细胞移植到33D1+DC耗竭小鼠的真皮内，皮下注射脂多糖一次或两次对已建立的肿瘤生长有明显的抑制作用。经静脉注射的B16-F10黑色素瘤细胞，经两次脂多糖刺激后，肺组织中NK1.1+CD3−NK细胞的实际细胞数明显增加，从而抑制了小鼠肺转移的发生。此外，腹腔注射极少量的马法兰(L-苯丙氨酸芥末；L-PAM)(0.25g/kg)给脂多糖刺激的33D1+DC缺失小鼠，有助于在肿瘤浸润性淋巴细胞中诱导H-2kb限制性表位特异性CD8+细胞毒性T淋巴细胞(CTL)，以对抗已建立的同基因E.G7-OVA淋巴瘤。这些发现表明，在体内选择性靶向特定的DC亚群，如DEC-205+DC或与极少量的抗癌药物一起激活CD8+CTL和NK效应器的重要性和有效性，为肿瘤免疫治疗提供了新的方向。
Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1+ and DEC-205+ DCs. Using anti-33D1-specific monoclonal antibody, 33D1+ DCs were successfully depleted from C57BL/6 mice. When 33D1+ DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be mediated by the remaining DEC-205+ DCs was markedly enhanced, which may induce Th1 dominancy upon TLR signaling. The 33D1+ DC-depleted mice, implanted with syngeneic Hepa1-6 hepatoma or B16-F10 melanoma cells into the dermis, showed apparent inhibition of already established tumor growth in vivo when they were subcutaneously (sc) injected once or twice with LPS after tumor implantation. Moreover, the development of lung metastasis of B16-F10 melanoma cells injected intravenously was also suppressed when 33D1+ DC-deleted mice were stimulated twice with LPS in a similar manner, in which the actual cell number of NK1.1+CD3− NK cells in lung tissues was markedly increased. Furthermore, intraperitoneal (ip) administration of a very small amount of melphalan (l-phenylalanine mustard; l-PAM) (0.25 mg/kg) in LPS-stimulated 33D1+ DC-deleted mice helped to induce H-2Kb-restricted epitope-specific CD8+ cytotoxic T lymphocytes (CTLs) among tumor-infiltrating lymphocytes against already established syngeneic E.G7-OVA lymphoma. These findings indicate the importance and effectiveness of selective targeting of a specific subset of DCs, such as DEC-205+ DCs alone or with a very small amount of anticancer drugs to activate both CD8+ CTLs and NK effectors without externally added tumor antigen stimulation in vivo and provide a new direction for tumor immunotherapy.
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影响因子：
82.9
作者：
Fernandez, NC;Lozier, A;Zitvogel, L
通讯作者：
Zitvogel, L
影响因子：
4.4
作者：
Fujimoto, C;Nakagawa, Y;Takahashi, H
通讯作者：
Takahashi, H
DOI：
10.1073/pnas.0711976105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Trumpfheller, Christine;Caskey, Marina;Steinman, Ralph M.
通讯作者：
Steinman, Ralph M.
DOI：
10.1084/jem.121.1.171
发表时间：
1965-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
ROWE DS;FAHEY JL
通讯作者：
FAHEY JL
影响因子：
4.4
作者：
Wakabayashi, Ayako;Nakagawa, Yohko;Takahashi, Hidemi
通讯作者：
Takahashi, Hidemi