Hua Li, Fang Mingli, Dong Boqi, Guo Sheng, Cui Cuiyun, Liu Jiwei, Yao Yun, Xiao Yue, Li Xin, Ren Yunjia, Meng Xiuping, Hao Xu, Zhao Peiyan, Song Yilan, Wang Liying, Yu Yongli
Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, China.
Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, China.
Oncotarget. 2016 Dec 13;7(50):82369-82383. doi: 10.18632/oncotarget.10693.
Allogeneic tumors are eventually rejected by adaptive immune responses, however, little is known about how allogeneic tumors are eradicated at the early stage of tumor development. In present study, we found that NKG2DL low expressing cancer cells were developed into palpable allogeneic tumors in mice within a week after the inoculation, while NKG2DL high expressing cancer cells failed to. The NKG2DL high expressing cancer cells could increase NKG2D+ NK cells in the allogeneic mice after being inoculated for 3 days. Artificially up-regulating NKG2DL on cancer cells with low level expressed NKG2DL by a CpG ODN resulted in the retardation and rejection of the allogeneic tumors at the early stage. The contribution of up-regulated NKG2DL to the early rejection was further confirmed by the results that the development of allogeneic tumors from cancer cells transfected with NKG2DL genes was significantly inhibited in mice at the early stage. Overall, hopefully, the data may provide insights for combining the allogeneic NK cell adoptive transfer with the approaches of up-regulating NKG2DL to treat cancer patients.
异基因肿瘤最终会被适应性免疫反应排斥,然而,关于异基因肿瘤在肿瘤发展早期是如何被根除的,人们知之甚少。在本研究中,我们发现,接种后一周内,NKG2DL低表达的癌细胞在小鼠体内发展成可触及的异基因肿瘤,而NKG2DL高表达的癌细胞则未能如此。接种3天后,NKG2DL高表达的癌细胞可增加异基因小鼠体内NKG2D+NK细胞的数量。通过CpG ODN人工上调NKG2DL低表达癌细胞上的NKG2DL,导致异基因肿瘤在早期出现生长迟缓并被排斥。用NKG2DL基因转染的癌细胞在小鼠体内早期形成异基因肿瘤的过程受到显著抑制,这一结果进一步证实了上调的NKG2DL对早期排斥反应的作用。总体而言,有望这些数据可为将异基因NK细胞过继性转移与上调NKG2DL的方法相结合来治疗癌症患者提供思路。