Allogeneic dendritic cells induce potent antitumor immunity by activating KLRG1+CD8 T cells

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作者
Chao Wang
Zhengyuan Li
Zhongli Zhu
Yijie Chai
Yiqing Wu
Zhenglong Yuan
Zhijie Chang
Zhao Wang
Minghui Zhang
机构
[1] Tsinghua University,School of Medicine
[2] The Second Affiliated Hospital of Shandong First Medical University,Department of Clinical Laboratory
[3] Tsinghua University,State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences
[4] Tsinghua University,Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences
[5] The First Hospital of Tsinghua University,The Central Laboratory
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Scientific Reports | / 9卷
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摘要
The graft-versus-leukemia effect reminds us to observe the allogeneic cell elicited anti-tumor immune responses. Here we immunized recipient B6 mice with different types of allogenic leukocytes and found that vaccination with allogenic dendritic cells (alloDC) elicited the most efficient protection against broad-spectrum tumors. The recipient lymphocytes were analyzed and the data showed that CD8 T cells increased significantly after immunization and expressed effector memory T cell marker KLRG1. Functional evaluation demonstrated that these KLRG1+CD8 T cells could kill tumor cells in vitro and in vivo in Granzyme B- and Fas/FasL-dependent manners with no tumor antigen specificity, and tend to migrate into tumor sites by high expression of heparanase. Adoptive transfer of these cells could provide antitumor protection against tumors. AlloDC could also treat mice with residual tumors and combination of anti-PD1 antibody could enhance this effects. Together, our study showed that alloDC-immunization could induce potent antitumor effect through the expansion of KLRG1+CD8 T cells, which can work as both preventive and therapeutic tumor vaccines.
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