Activation of tolerogenic dendritic cells in the tumor draining lymph nodes by CD8+ T cells engineered to express CD40 ligand.
Activation of tolerogenic dendritic cells in the tumor draining lymph nodes by CD8+ T cells engineered to express CD40 ligand.
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通过设计表达 CD40 配体的 CD8+ T 细胞激活肿瘤引流淋巴结中的耐受性树突状细胞。
DOI：
10.4049/jimmunol.0903111
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Higham EM;Wittrup KD;Chen J
肿瘤微环境中的致耐受性树突状细胞可以抑制强抗肿瘤T细胞应答的产生和维持。在此，我们研究了肿瘤反应性CD 8 + T细胞局部递送CD 40配体（CD 40 L）对小鼠前列腺转基因腺癌（TRAMP）模型中树突状细胞活化和抗肿瘤T细胞应答的影响。为了增加免疫刺激信号，通过删除大部分胞质结构域来工程化CD 40 L，以增加其在CD 8 + T细胞表面上的表达水平和持续时间。表达截短形式的CD 40 L的肿瘤反应性CD 8 + T细胞刺激体外树突状细胞和体内前列腺引流淋巴结（PDLN）中树突状细胞的成熟。树突状细胞成熟后，显著更高比例的过继转移的肿瘤反应性（报告）CD 8 + T细胞被刺激表达IFN-γ并浸润前列腺组织。如果TRAMP小鼠也用肿瘤特异性抗原免疫，则抗肿瘤CD 8 + T细胞应答进一步增强。这些发现表明，增强的T细胞反应可以通过工程化肿瘤反应性T细胞来实现，以将刺激信号传递到肿瘤微环境中的树突状细胞。这是作者制作的手稿版本，已被《免疫学杂志》（The JI）接受出版。美国免疫学家协会(AAI)JI的出版商拥有本手稿的版权。这份手稿尚未由联合执行机构进行编辑或编辑校对;因此可能与联合执行机构（在线和印刷版）公布的最终版本不同。AAI（JI）对作者制作的手稿版本或美国国立卫生研究院或任何其他第三方从中衍生的任何版本中的错误或遗漏不承担责任。记录的最终可引用版本可在www.jimmunol.org上找到。
Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust anti-tumor T cell responses. Here, we investigated the effects of local delivery of CD40 ligand (CD40L) by tumor-reactive CD8+ T cells on dendritic cell activation and anti-tumor T cell responses in the TRansgenic Adenocarcimona of the Mouse Prostate (TRAMP) model. To increase the immunostimulatory signal, CD40L was engineered, by deleting the majority of the cytoplasmic domain, to increase both its level of expression and duration on the surface of CD8+ T cells. Tumor-reactive CD8+ T cells expressing the truncated form of CD40L stimulated maturation of dendritic cells in vitro and in the prostate draining lymph nodes (PDLN) in vivo. Following dendritic cell maturation, a significantly higher fraction of adoptively transferred, tumor-reactive (reporter) CD8+ T cells was stimulated to express IFN-γ and infiltrate the prostate tissue. The anti-tumor CD8+ T cell response was further enhanced if TRAMP mice were also immunized with a tumor-specific antigen. These findings demonstrate that augmented T cell responses can be achieved by engineering tumor-reactive T cells to deliver stimulatory signals to dendritic cells in the tumor microenvironment. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the United States National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.
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DOI：
10.1073/pnas.95.9.5205
发表时间：
1998-04-28
影响因子：
11.1
作者：
Kornbluth, RS;Kee, K;Richman, DD
通讯作者：
Richman, DD
DOI：
10.1073/pnas.0503726102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Klebanoff, CA;Gattinoni, L;Restifo, NP
通讯作者：
Restifo, NP
影响因子：
20.3
作者：
Menetrier-Caux, C;Montmain, G;Blay, JY
通讯作者：
Blay, JY
影响因子：
82.9
作者：
Mauri, C;Mars, LT;Londei, M
通讯作者：
Londei, M
影响因子：
2.6
作者：
Geldart, T;Illidge, T
通讯作者：
Illidge, T