共 42 条
Allogeneic dendritic cells induce potent antitumor immunity by activating KLRG1+CD8 T cells
被引:9
作者:
Wang, Chao
[1
,4
]
Li, Zhengyuan
[1
]
Zhu, Zhongli
[2
]
Chai, Yijie
[1
]
Wu, Yiqing
[1
]
Yuan, Zhenglong
[1
]
Chang, Zhijie
[3
]
Wang, Zhao
[4
]
Zhang, Minghui
[1
,5
]
机构:
[1] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
[2] Shandong First Med Univ, Affiliated Hosp 2, Dept Clin Lab, Tai An 271000, Shandong, Peoples R China
[3] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Sch Med, Sch Life Sci, Beijing 100084, Peoples R China
[4] Tsinghua Univ, Prot Sci Key Lab, Minist Educ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China
[5] Tsinghua Univ, Hosp 1, Cent Lab, Beijing 100084, Peoples R China
基金:
中国国家自然科学基金;
关键词:
SECRETING TUMOR VACCINE;
VERSUS-HOST-DISEASE;
KILLER-CELLS;
CANCER;
SAFETY;
TRANSPLANTATION;
IPILIMUMAB;
EXPRESSION;
EFFECTOR;
TRIAL;
D O I:
10.1038/s41598-019-52151-3
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
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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