Anti-CD40-induced inflammatory E-cadherin+ dendritic cells enhance T cell responses and antitumour immunity in murine Lewis lung carcinoma.
Anti-CD40-induced inflammatory E-cadherin+ dendritic cells enhance T cell responses and antitumour immunity in murine Lewis lung carcinoma.
复制标题
抗 CD40 诱导的炎症 E-钙粘蛋白树突状细胞增强小鼠 Lewis 肺癌中的 T 细胞反应和抗肿瘤免疫
DOI：
10.1186/s13046-015-0126-9
复制
发表时间：
2015-02-05
期刊：
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zhang Y;Hu X;Hu Y;Teng K;Zhang K;Zheng Y;Hong X;Yu K;Wang Y;Liu L
背景CD 40激动性抗体被证明可以激活抗原呈递细胞（APC）并增强抗肿瘤T细胞反应，从而为癌症免疫治疗提供了新的治疗选择。在激动性CD 40抗体介导的炎症反应中，已经鉴定了一种新的E-钙粘蛋白+树突状细胞（DC）亚群，但对这些DC在肿瘤免疫中的作用知之甚少。本研究探讨抗CD 40介导的炎性E-cadherin + DCs对小鼠刘易斯肺癌（LLC）的作用。通过促进效应CD 4 + T细胞、CEA特异性CD 8 + T细胞和CD 103 + CD 8 + T细胞的分化并评估它们对肿瘤攻击的抗性（包括肿瘤体积和存活曲线的变化）来评估E-cadherin + DC的体内抗肿瘤活性。我们证明，抗CD 40介导的E-cadherin +炎性DC在Rag 1 KO小鼠的肺中积聚，并且能够刺激幼稚的CD 4+细胞，T细胞诱导Th 1和Th 17细胞分化和极化，并抑制调节性T细胞和Th 2应答。重要的是，随着E-钙粘蛋白+DC过继转移到刘易斯肺癌模型中，炎性DC增加了Th 1和Th 17细胞应答，降低了Treg细胞和Th 2应答。有趣的是，在注射炎性E-钙粘蛋白+DC后，结论抗CD 40诱导的E-cadherin + DCs能增强非小细胞肺癌（NSCLC）小鼠的T细胞免疫应答和抗肿瘤活性，可用于增强DC-103 + CD 8 + T细胞和CEA-特异性CD 8 + T细胞的抗肿瘤作用。基于肽的针对非小细胞肺癌的疫苗。
BackgroundAgonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells (DCs) has been identified, and little is known about the role of these DCs in tumour immunity. This study investigated the effect of anti-CD40-mediated inflammatory E-cadherin + DCs in murine Lewis lung carcinoma (LLC).MethodsThe phenotype and characteristics of anti-CD40-mediated inflammatory E-cadherin + DCs isolated from the anti-CD40 model were assessed in vitro. The antitumour activity of E-cadherin + DCs were evaluated in vivo by promoting the differentiation of effector CD4+ T cells, CEA-specific CD8+ T cells and CD103+ CD8+ T cells and assessing their resistance to tumour challenge, including variations in tumour volume and survival curves.ResultsHere, we demonstrated that anti-CD40-mediated E-cadherin + inflammatory DCs accumulate in the lungs of Rag1 KO mice and were able to stimulate naïve CD4+ T cells to induce Th1 and Th17 cell differentiation and polarisation and to inhibit regulatory T cell and Th2 responses. Importantly, with the adoptive transfer of E-cadherin + DCs into the Lewis lung cancer model, the inflammatory DCs increased the Th1 and Th17 cell responses and reduced the Treg cell and Th2 responses. Interestingly, following the injection of inflammatory E-cadherin + DCs, the CD103+ CD8+ T cell and CEA-specific CD8+ T cell responses increased and exhibited potent antitumour immunity.ConclusionsThese findings indicate that anti-CD40-induced E-cadherin + DCs enhance T cell responses and antitumour activity in non-small cell lung cancer (NSCLC)-bearing mice and may be used to enhance the efficacy of DC-based peptide vaccines against NSCLC.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Siddiqui KR;Laffont S;Powrie F
通讯作者：
Powrie F
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
影响因子：
32.4
作者：
DIGHE, AS;RICHARDS, E;SCHREIBER, RD
通讯作者：
SCHREIBER, RD
影响因子：
64.8
作者：
Grivennikov, Sergei I.;Wang, Kepeng;Mucida, Daniel;Stewart, C. Andrew;Schnabl, Bernd;Jauch, Dominik;Taniguchi, Koji;Yu, Guann-Yi;Oesterreicher, Christoph H.;Hung, Kenneth E.;Datz, Christian;Feng, Ying;Fearon, Eric R.;Oukka, Mohamed;Tessarollo, Lino;Coppola, Vincenzo;Yarovinsky, Felix;Cheroutre, Hilde;Eckmann, Lars;Trinchieri, Giorgio;Karin, Michael
通讯作者：
Karin, Michael