Attribution of NKG2DL to the inhibition of early stage allogeneic tumors in mice

Li Hua; Mingli Fang; Boqi Dong; Sheng Guo; Cuiyun Cui; Jiwei Liu; Yun Yao; Yue Xiao; Xin Li; Yunjia Ren; Xiuping Meng; Xu Hao; Peiyan Zhao; Yilan Song; Liying Wang; Yongli Yu

doi:10.18632/oncotarget.10693

Attribution of NKG2DL to the inhibition of early stage allogeneic tumors in mice

Oncotarget. 2016 Dec 13;7(50):82369-82383. doi: 10.18632/oncotarget.10693.

Authors

Li Hua¹, Mingli Fang², Boqi Dong¹, Sheng Guo², Cuiyun Cui¹, Jiwei Liu², Yun Yao², Yue Xiao², Xin Li², Yunjia Ren², Xiuping Meng¹, Xu Hao¹, Peiyan Zhao², Yilan Song¹, Liying Wang², Yongli Yu¹

Affiliations

¹ Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, China.
² Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, China.

Abstract

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.

Keywords: NK cells; NKG2D+ cells; NKG2DL; allogeneic tumors; early stage.

Publication types

Comparative Study

MeSH terms

Animals
Brain Neoplasms / genetics
Brain Neoplasms / immunology
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Line, Tumor
Cell Proliferation*
Female
Glioma / genetics
Glioma / immunology
Glioma / metabolism*
Glioma / pathology
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / metabolism
Killer Cells, Natural / immunology
Killer Cells, Natural / metabolism
Mammary Neoplasms, Experimental / genetics
Mammary Neoplasms, Experimental / immunology
Mammary Neoplasms, Experimental / metabolism*
Mammary Neoplasms, Experimental / pathology
Melanoma, Experimental / genetics
Melanoma, Experimental / immunology
Melanoma, Experimental / metabolism*
Melanoma, Experimental / pathology
Membrane Proteins
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred ICR
NK Cell Lectin-Like Receptor Subfamily K / genetics
NK Cell Lectin-Like Receptor Subfamily K / immunology
NK Cell Lectin-Like Receptor Subfamily K / metabolism*
Neoplasm Transplantation
Signal Transduction
Skin Neoplasms / genetics
Skin Neoplasms / immunology
Skin Neoplasms / metabolism*
Skin Neoplasms / pathology
Time Factors
Transfection
Transplantation, Homologous
Transplantation, Isogeneic
Tumor Burden

Substances

Carrier Proteins
Histocompatibility Antigens Class I
Klrk1 protein, mouse
Membrane Proteins
NK Cell Lectin-Like Receptor Subfamily K
UL16 binding protein 1, mouse