The R132H mutation in IDH1 promotes the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis and is correlated with a better prognosis in gliomas

被引:60
作者
Ren, Feifei [1 ,2 ]
Zhao, Qitai [1 ]
Huang, Lan [1 ]
Zheng, Yujia [1 ]
Li, Lifeng [1 ]
He, Qianyi [1 ,3 ]
Zhang, Chaoqi [1 ]
Li, Feng [1 ]
Maimela, Nomathamsanqa R. [1 ]
Sun, Zhi [4 ]
Jia, Qingquan [4 ]
Ping, Yu [1 ]
Zhang, Zhen [1 ]
Chen, Xinfeng [1 ]
Yue, Ying [1 ,5 ]
Liu, Shasha [1 ]
Cao, Ling [1 ]
Zhang, Yi [1 ,2 ,6 ,7 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Biotherapy Ctr, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Sch Life Sci, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, Zhengzhou 450052, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Dept Pharm, Zhengzhou 450052, Henan, Peoples R China
[5] 7 Peoples Hosp Zhengzhou, Zhengzhou 450052, Henan, Peoples R China
[6] Zhengzhou Univ, Affiliated Hosp 1, Canc Ctr, Zhengzhou 450052, Henan, Peoples R China
[7] Henan Key Lab Tumor Immunol & Biotherapy, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
CX3CL1; gliomas; IDH1-R132H; NK cells; p-NF-kappa B; NF-KAPPA-B; CHEMOKINE RECEPTORS; IMMUNE-SYSTEM; TNF-ALPHA; CANCER; PROLIFERATION; CLASSIFICATION; RELEVANCE; CX3CL1; MICROENVIRONMENT;
D O I
10.1111/imcb.12225
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mutations in the isocitrate dehydrogenase (IDH) 1 gene, especially the R132H mutation, have been reported to be associated with a better prognosis in glioma patients. However, the underlying molecular mechanisms are not yet well understood. Many factors may contribute to differences in the survival of IDH1 wild-type and IDH1 mutant glioma patients, in which immune components play a potentially important role. In this study, we analyzed The Cancer Genome Atlas (TCGA), and the Chinese Glioma Genome Atlas (CGGA) databases, as well as glioma patient-derived tumor samples. We found that there was a higher infiltration of natural killer (NK) cells in IDH1 mutant glioma patients, and this was correlated with a better prognosis. We also showed that IDH1-R132 tumor cells had higher expression levels of the chemokine CX3CL1. This arises as a result of the conversion of alpha-ketoglutarate to R(-)-2-hydroxyglutarate by the IDH1 mutant and the resultant phosphorylation of nuclear factor kappa B. Knockdown of CX3CL1 decreased the migration of NK cells. In addition, the high levels of expression of CX3CL1 were positively correlated with glioma patient survival in the TCGA and CGGA databases, and in the clinical samples. Overall, our data have identified a novel mechanism in which R132H mutation of the IDH1 gene serves as a tumor suppressor by promoting the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis.
引用
收藏
页码:457 / 469
页数:13
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